Pain, Postoperative, Surgical Procedure, Unspecified
Conditions
Keywords
Laparoscopy, Robotic Surgical Procedures, Hysterectomy, Anesthetics, Local, Bupivacaine, Pain, Postoperative
Brief summary
The investigators are studying ways to improve pain control after surgery. One way to decrease pain is to inject incisions with a numbing medicine (local anesthetic) while in the operating room. There is an FDA approved extended-release version of a commonly used local anesthetic (bupivacaine) that can last for 4 days instead of 6 hours. The investigators are studying whether using the extended-release medication (Exparel) will give better pain relief after laparoscopic and robotic-assisted hysterectomies.
Detailed description
Lidocaine and bupivacaine hydrochloride (HCl) are the most commonly used drugs for wound infiltration during laparoscopic surgery for post-operative pain control. There is some evidence that wound infiltration decreases immediate post-operative pain. While bupivacaine has a slightly slower onset of action (5-10 minutes), it has become the preferred injectable anesthetic for surgical use because of its longer duration of effect (4-8 hours versus 1-2 hours for lidocaine). DepoFoam bupivacaine (EXPAREL, Pacira Pharmaceuticals, Inc., Parsippany, NJ, USA) is a newer extended-release formulation of bupivacaine HCl approved by the U.S. Federal Drug Administration in October 2011. In this suspension, bupivacaine is encapsulated in microscopic spherical lipid-based particles of varying size to allow dispersion of the drug over an extended period of time. Analgesia is prolonged up to 96 hours. Given the extended duration of action, this liposomal bupivacaine may be better at providing post-operative pain relief in laparoscopic surgery. Phase three trials have shown better pain control in the first 24 hours and less opioid use overall in bunionectomies, hemorrhoidectomies, and total knee replacement surgery when compared to placebo. No studies, however, have been published evaluating extended-release liposomal bupivacaine for laparoscopic surgery, or gynecologic surgery in general. Currently, we are using liposomal bupivacaine for pain relief after laparoscopic hysterectomies, but as stated, it has never been formally evaluated. We hypothesize that liposomal bupivacaine (extended-release) provides extended pain relief and decreases the need for supplemental opioid use after major laparoscopic surgery. We will be evaluating whether pre-incision infiltration of extended-release bupivacaine decreases post-operative pain from laparoscopic and robotic-assisted hysterectomy compared to bupivacaine HCl (short-acting). To achieve this evaluation we designed a double-blinded randomized controlled trial. Patients who are scheduled to undergo a laparoscopic or robotic-assisted hysterectomy will be invited to participate. Group A will receive pre-incision infiltration of each trocar site with 4 ml of 0.25% Bupivacaine HCl. Group B will receive pre-incision infiltration of each trocar site with 4 ml of extended-release bupivacaine (EXPAREL) (13.3mg/ml). Subjects and outcome assessors will be blinded to group allocation. Data will be collected while patients are in the hospital on pain levels and consumption of opioid pain medications. Upon discharge, pain levels, functioning, and quantity of opioid and non-steroidal anti-inflammatory (NSAID) pain medications will be collected through online questionnaires. Subjects will be followed until their 2-3 weeks post-operative visit.
Interventions
DRUGLiposomal Bupivacaine
pre-incision infiltration with liposomal bupivacaine
DRUGBupivacaine HCl
pre-incision infiltration with bupivacaine HCl
Sponsors
AdventHealth
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Benign indication for surgery 2. Planned multiport laparoscopic or robotic assisted hysterectomy 3. Non-pregnant 4. Able to provide informed consent 5. Owns smartphone or computer with internet access 6. Willing to provide contact phone number and accept SMS text messages 7. Ability to speak and read English (because texts and online surveys will be in English only)
Exclusion criteria
1. Planned additional procedures (e.g. incontinence surgery, prolapse repair or bowel surgery) 2. Contraindication to study drug 1. Severe Hepatic disease 2. Severe Kidney disease 3. Current use of monoamine oxidase inhibitors 4. Current use of tricyclic antidepressants 3. History of substance or alcohol abuse within the past 2 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Numerical Rating Scale (NRS) Post-operative Pain Score on Post-Operative Day 1 (POD1). | 24 hours | Numerical Rating Scale (0-10) post-operative pain score on POD1, where 0 = no pain and 10 = worst pain imaginable |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| NRS Pain Score at 4 Hours | 4 hours post-op | Pain scale measured from 0-10, where 0 = no pain and 10 = worst pain imaginable |
| NRS Pain Score at 8 Hours | 8 hours post-op | Pain scale (0-10), where 0 = no pain and 10 = worst pain imaginable |
| NRS Pain Score at 16 Hours | 16 hours post-op | Pain scale (0-10), where 0 = no pain and 10 = worst pain imaginable |
| NRS Pain Score Post-op Day 2 | 2 days post-op | Pain scale (0-10), where 0 = no pain and 10 = worst pain imaginable |
| NRS Pain Score Post-op Day 3 | 3 days post-op | Pain scale, where 0 = no pain and 10 = worst pain imaginable |
| NRS Pain Score at 2 Hours | 2 hours post-op | numeric rating scale (0-10), mean and SD, where 0 = no pain and 10 = worst pain imaginable |
| Quality of Life as Measured by the Brief Pain Inventory (BPI) | Post-Operative Day 2 | The brief pain inventory scale uses the 0 to 10 numerical rating scale to measure pain intensity under four different conditions. On the four conditions 0 = no pain, no relief, and does not interfere, whereas 10 = pain as bad as you can imagine, complete relief, and completely interferes |
| Total Opioid Use Prior to Hospital Discharge | 24 hours | Oral morphine equivalent of opioid use while in the hospital |
| Total Opioid Use End of Post-op Day 3 | 72 hrs post-op | Total use of home opioids by pill count/ oral morphine equivalents |
| Total Opioid Use at Post-op Day 14 | Post-Operative Day 14 | Total use of home opioids by pill count/ oral morphine equivalents |
| Number of Participants With Adverse Events | Post-Operative Day 14 | — |
| NRS Pain Score Post-op Day 14 | Post-Operative Day 14 | Pain scale (0-10), where 0 = no pain and 10 = worst pain imaginable |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Liposomal Bupivacaine extended-release bupivacaine (EXPAREL)
Liposomal Bupivacaine: pre-incision infiltration with liposomal bupivacaine | 32 |
| Bupivacaine HCl short-acting bupivacaine
Bupivacaine HCl: pre-incision infiltration with bupivacaine HCl | 32 |
| Total | 64 |
Baseline characteristics
| Characteristic | Liposomal Bupivacaine | Bupivacaine HCl | Total |
|---|---|---|---|
| Age, Continuous | 45 years STANDARD_DEVIATION 8.6 | 45.4 years STANDARD_DEVIATION 9.1 | 45.19 years STANDARD_DEVIATION 8.86 |
| BMI | 29 kg/m^2 | 27.6 kg/m^2 | 28.3 kg/m^2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 8 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 4 Participants | 8 Participants |
| Race (NIH/OMB) White | 24 Participants | 18 Participants | 42 Participants |
| Region of Enrollment United States | 32 Participants | 32 Participants | 64 Participants |
| Sex: Female, Male Female | 32 Participants | 32 Participants | 64 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 | 0 / 32 | 0 / 32 |
| other Total, other adverse events | 0 / 32 | 0 / 32 |
| serious Total, serious adverse events | 0 / 32 | 0 / 32 |
Outcome results
Primary
Numerical Rating Scale (NRS) Post-operative Pain Score on Post-Operative Day 1 (POD1).
Numerical Rating Scale (0-10) post-operative pain score on POD1, where 0 = no pain and 10 = worst pain imaginable
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liposomal Bupivacaine | Numerical Rating Scale (NRS) Post-operative Pain Score on Post-Operative Day 1 (POD1). | 4.17 units on a scale | Standard Deviation 2.2 |
| Bupivacaine HCl | Numerical Rating Scale (NRS) Post-operative Pain Score on Post-Operative Day 1 (POD1). | 4.97 units on a scale | Standard Deviation 2.6 |
Secondary
NRS Pain Score at 16 Hours
Pain scale (0-10), where 0 = no pain and 10 = worst pain imaginable
Time frame: 16 hours post-op
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liposomal Bupivacaine | NRS Pain Score at 16 Hours | 3.1 score on a scale | Standard Deviation 3.18 |
| Bupivacaine HCl | NRS Pain Score at 16 Hours | 3.97 score on a scale | Standard Deviation 2.76 |
Secondary
NRS Pain Score at 2 Hours
numeric rating scale (0-10), mean and SD, where 0 = no pain and 10 = worst pain imaginable
Time frame: 2 hours post-op
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liposomal Bupivacaine | NRS Pain Score at 2 Hours | 2.53 units on a scale | Standard Deviation 2.53 |
| Bupivacaine HCl | NRS Pain Score at 2 Hours | 2.74 units on a scale | Standard Deviation 3.24 |
Secondary
NRS Pain Score at 4 Hours
Pain scale measured from 0-10, where 0 = no pain and 10 = worst pain imaginable
Time frame: 4 hours post-op
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liposomal Bupivacaine | NRS Pain Score at 4 Hours | 3.87 Score on a scale | Standard Deviation 2.86 |
| Bupivacaine HCl | NRS Pain Score at 4 Hours | 3 Score on a scale | Standard Deviation 2.95 |
Secondary
NRS Pain Score at 8 Hours
Pain scale (0-10), where 0 = no pain and 10 = worst pain imaginable
Time frame: 8 hours post-op
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liposomal Bupivacaine | NRS Pain Score at 8 Hours | 3.77 Score on a scale | Standard Deviation 2.75 |
| Bupivacaine HCl | NRS Pain Score at 8 Hours | 3.67 Score on a scale | Standard Deviation 3.01 |
Secondary
NRS Pain Score Post-op Day 14
Pain scale (0-10), where 0 = no pain and 10 = worst pain imaginable
Time frame: Post-Operative Day 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liposomal Bupivacaine | NRS Pain Score Post-op Day 14 | 1.64 score on a scale | Standard Deviation 2.58 |
| Bupivacaine HCl | NRS Pain Score Post-op Day 14 | 2.07 score on a scale | Standard Deviation 2.58 |
Secondary
NRS Pain Score Post-op Day 2
Pain scale (0-10), where 0 = no pain and 10 = worst pain imaginable
Time frame: 2 days post-op
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liposomal Bupivacaine | NRS Pain Score Post-op Day 2 | 3.34 score on a scale | Standard Deviation 2.06 |
| Bupivacaine HCl | NRS Pain Score Post-op Day 2 | 4.17 score on a scale | Standard Deviation 2.16 |
Secondary
NRS Pain Score Post-op Day 3
Pain scale, where 0 = no pain and 10 = worst pain imaginable
Time frame: 3 days post-op
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liposomal Bupivacaine | NRS Pain Score Post-op Day 3 | 2.79 score on a scale | Standard Deviation 2.26 |
| Bupivacaine HCl | NRS Pain Score Post-op Day 3 | 4.07 score on a scale | Standard Deviation 1.98 |
Secondary
Number of Participants With Adverse Events
Time frame: Post-Operative Day 14
Population: if a patient reported a particular adverse effect at more than one time point, the patient was counted only once. Patients may report more than one adverse effect. Analysis and percentages reflect only those with complaints of adverse effects.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Liposomal Bupivacaine | Number of Participants With Adverse Events | Gas distension/bloated | 5 Participants |
| Liposomal Bupivacaine | Number of Participants With Adverse Events | Constipation | 5 Participants |
| Liposomal Bupivacaine | Number of Participants With Adverse Events | Nausea | 4 Participants |
| Liposomal Bupivacaine | Number of Participants With Adverse Events | Headache | 2 Participants |
| Liposomal Bupivacaine | Number of Participants With Adverse Events | Sore throat/cough | 1 Participants |
| Liposomal Bupivacaine | Number of Participants With Adverse Events | Dizziness | 1 Participants |
| Bupivacaine HCl | Number of Participants With Adverse Events | Sore throat/cough | 3 Participants |
| Bupivacaine HCl | Number of Participants With Adverse Events | Gas distension/bloated | 9 Participants |
| Bupivacaine HCl | Number of Participants With Adverse Events | Headache | 7 Participants |
| Bupivacaine HCl | Number of Participants With Adverse Events | Constipation | 2 Participants |
| Bupivacaine HCl | Number of Participants With Adverse Events | Dizziness | 3 Participants |
| Bupivacaine HCl | Number of Participants With Adverse Events | Nausea | 6 Participants |
Secondary
Quality of Life as Measured by the Brief Pain Inventory (BPI)
The brief pain inventory scale uses the 0 to 10 numerical rating scale to measure pain intensity under four different conditions. On the four conditions 0 = no pain, no relief, and does not interfere, whereas 10 = pain as bad as you can imagine, complete relief, and completely interferes
Time frame: Post-Operative Day 3
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liposomal Bupivacaine | Quality of Life as Measured by the Brief Pain Inventory (BPI) | 3.36 score on a scale | Standard Deviation 2.71 |
| Bupivacaine HCl | Quality of Life as Measured by the Brief Pain Inventory (BPI) | 3.94 score on a scale | Standard Deviation 2.37 |
Secondary
Quality of Life as Measured by the Brief Pain Inventory (BPI)
at time of post-op visit The brief pain inventory scale uses the 0 to 10 numerical rating scale to measure pain intensity under four different conditions. On the four conditions 0 = no pain, no relief, and does not interfere, whereas 10 = pain as bad as you can imagine, complete relief, and completely interferes
Time frame: Post-Operative Day 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liposomal Bupivacaine | Quality of Life as Measured by the Brief Pain Inventory (BPI) | 1.74 score on a scale | Standard Deviation 2.61 |
| Bupivacaine HCl | Quality of Life as Measured by the Brief Pain Inventory (BPI) | 1.65 score on a scale | Standard Deviation 1.93 |
Secondary
Quality of Life as Measured by the Brief Pain Inventory (BPI)
The brief pain inventory scale uses the 0 to 10 numerical rating scale to measure pain intensity under four different conditions. On the four conditions 0 = no pain, no relief, and does not interfere, whereas 10 = pain as bad as you can imagine, complete relief, and completely interferes
Time frame: Post-Operative Day 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liposomal Bupivacaine | Quality of Life as Measured by the Brief Pain Inventory (BPI) | 4.09 score on a scale | Standard Deviation 2.58 |
| Bupivacaine HCl | Quality of Life as Measured by the Brief Pain Inventory (BPI) | 4.31 score on a scale | Standard Deviation 1.99 |
Secondary
Total Opioid Use at Post-op Day 14
Total use of home opioids by pill count/ oral morphine equivalents
Time frame: Post-Operative Day 14
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Liposomal Bupivacaine | Total Opioid Use at Post-op Day 14 | 360 mg (oral morphine equivalents) |
| Bupivacaine HCl | Total Opioid Use at Post-op Day 14 | 443 mg (oral morphine equivalents) |
Secondary
Total Opioid Use End of Post-op Day 3
Total use of home opioids by pill count/ oral morphine equivalents
Time frame: 72 hrs post-op
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Liposomal Bupivacaine | Total Opioid Use End of Post-op Day 3 | 320 mg (oral morphine equivalents) |
| Bupivacaine HCl | Total Opioid Use End of Post-op Day 3 | 344 mg (oral morphine equivalents) |
Secondary
Total Opioid Use Prior to Hospital Discharge
Oral morphine equivalent of opioid use while in the hospital
Time frame: 24 hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Liposomal Bupivacaine | Total Opioid Use Prior to Hospital Discharge | 216 mg (oral morphine equivalents) |
| Bupivacaine HCl | Total Opioid Use Prior to Hospital Discharge | 266 mg (oral morphine equivalents) |