Vaginal Hysterectomy
Conditions
Brief summary
The aim of this study is to compare the effects of preemptive analgesia using liposomal bupivacaine mixed with bupivacaine HCl, versus bupivacaine HCl alone for uterosacral ligament injection in patients undergoing vaginal hysterectomy. We hypothesize that the group receiving a combination of liposomal bupivacaine and bupivacaine HCl will report superior postoperative pain management. Enhancement in pain control should confer a decrease in opioid and other analgesic medication requirements, which may contribute to decreased nausea, vomiting, and higher overall patient satisfaction with pain control.
Detailed description
Prior to surgery, patients are assigned by chance (like a coin toss) to receive either the bupivacaine HCl injection at the time of surgery or bupivacaine HCl plus liposomal bupivacaine. Patients and the Principal Investigator cannot choose the study group. Patients will have a 50% chance of being assigned to either group; however, regardless of which group they are assigned to, the medical record will show that they received liposomal bupivacaine. The injections will be given in the vaginal area when the patient is under anesthesia. After surgery, patients will be asked to record their pain, medication use, pain scores and symptoms in a diary for each 12 hour interval up to 72 hours. Someone will also call twice a day during the 72 hours after surgery to ask about pain level and pain medication use. Patients will also receive a phone call 7-10 days after the surgery to ask about their recovery and pain level.
Interventions
DRUGLiposomal bupivacaine
Liposomal bupivacaine is a novel formulation of local bupivacaine and allows prolonged release of the medication, thereby providing longer lasting effects. It is approved by the FDA and has been shown to provide excellent pain control after surgery.
DRUGBupivacaine Hydrochloride
We currently administer local plain bupivacaine during vaginal hysterectomy to decrease pain in the postoperative period. Bupivacaine is an anesthetic that works by blocking nerve conduction and producing a numbing effect.
Sponsors
Pacira Pharmaceuticals, Inc
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
This will be a blinded study where investigators, patients, and care providers will be blinded to treatment assignment.
Intervention model description
Patients will be randomized to receive either the bupivacaine HCl injection at the time of surgery or bupivacaine HCl plus liposomal bupivacaine.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1\. Women 18-85 who will be having an outpatient vaginal hysterectomy with or without concurrent prolapse repair surgery at Mayo Clinic Hospital in Arizona
Exclusion criteria
1. Known history of hepatic (liver) disease as evidenced by an AST or ALT that is greater than normal values 2. Known history of renal (kidney) disease as evidenced by a serum creatinine that is greater than normal values 3. Known history of prolonged QT (QTc greater than 500 m/s) 4. Opiate tolerance as noted by daily use of greater than 20 mg morphine daily oral equivalents per day for a minimum of 1 month prior to surgery 5. Allergy or contraindication to amide local anesthetics, celecoxib, ketorolac, NSAIDs, acetaminophen, gabapentin, sulfa drugs, or ondansetron 6. Allergy to both oxycodone and hydromorphone 7. Patients with acute gastrointestinal bleed that has occurred less than 6 months prior to study enrollment 8. Adults lacking the ability to consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Post-surgical Opioid Medication Use | First 72 hours following surgery completion | Participants post-surgical analgesic medication use of IV hydrocodone and oxycodone measured in morphine equivalents (ME) |
| Total Post-surgical Analgesic Medication Use | First 72 hours following surgery completion | Participants post-surgical analgesic medication use of Ibuprofen and acetaminophen measured in milligrams (mg) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Nausea at 24, 48, and 72 Hours Post-surgery Completion | 24, 48, and 72 hours post-surgery | Number of times patient reported feeling nauseous |
| Emesis at 24, 48, and 72 Hours Post-surgery Completion | 24, 48, and 72 hours post-surgery | Number of times the patient vomited |
| Mean PACU Visual Analog Scale (VAS) (0-10) Pain Score | Assessed while patient in PACU for recovery post-surgery per standard procedure | Scale Ranges from 0 (no pain) to 10 (extreme pain) |
| Patient Satisfaction With Pain Management at 72 Hours and 7-10 Days Post Surgery | 72 hours and 7-10 days post surgery | Assessed on 0-10 scale (0 being worst level of satisfaction, 10 being best level) |
| Urinary Retention | At voiding trial prior to discharge from hospital, approximately 72 hours | Number of patients who had post-void residual (PVR) \>150cc's at voiding trial prior to discharge |
| VAS Pain Score at 24, 48, and 72 Hours Post-surgery Completion | 24, 48, and 72 hours post-surgery completion | Scale Ranges from 0 (no pain) to 10 (extreme pain) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standard Bupivacaine Patients in the control group will receive 0.25% bupivacaine hydrochloride (bupivacaine HCl). 10cc will be injected bilaterally into each uterosacral ligament prior to the colpotomy incision. After entry into the posterior cul-de-sac, an additional 10cc of will be injected bilaterally into the deeper uterosacral ligaments.
Bupivacaine Hydrochloride: We currently administer local plain bupivacaine during vaginal hysterectomy to decrease pain in the postoperative period. Bupivacaine is an anesthetic that works by blocking nerve conduction and producing a numbing effect. | 14 |
| Liposomal Bupivacaine Patients in the study group will receive a mixture of 0.5% bupivacaine HCl and liposomal bupivacaine in 1:1 ratio. 10cc of the mixture will be injected bilaterally into each uterosacral ligament prior to the colpotomy incision. After entry into the posterior cul-de-sac, an additional 10cc will be injected bilaterally into the deeper uterosacral ligaments
Liposomal bupivacaine: Liposomal bupivacaine is a novel formulation of local bupivacaine and allows prolonged release of the medication, thereby providing longer lasting effects. It is approved by the FDA and has been shown to provide excellent pain control after surgery.
Bupivacaine Hydrochloride: We currently administer local plain bupivacaine during vaginal hysterectomy to decrease pain in the postoperative period. Bupivacaine is an anesthetic that works by blocking nerve conduction and producing a numbing effect. | 14 |
| Total | 28 |
Baseline characteristics
| Characteristic | Liposomal Bupivacaine | Total | Standard Bupivacaine |
|---|---|---|---|
| Age, Continuous | 60.4 years STANDARD_DEVIATION 12.56 | 57.8 years STANDARD_DEVIATION 11.86 | 55.2 years STANDARD_DEVIATION 10.96 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 14 participants | 28 participants | 14 participants |
| Sex: Female, Male Female | 14 Participants | 28 Participants | 14 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 / 14 | 0 / 14 |
| other Total, other adverse events | 3 / 14 | 2 / 14 |
| serious Total, serious adverse events | 0 / 14 | 0 / 14 |
Outcome results
Primary
Total Post-surgical Analgesic Medication Use
Participants post-surgical analgesic medication use of Ibuprofen and acetaminophen measured in milligrams (mg)
Time frame: First 72 hours following surgery completion
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Standard Bupivacaine | Total Post-surgical Analgesic Medication Use | Ibuprofen | 5400.0 mg |
| Standard Bupivacaine | Total Post-surgical Analgesic Medication Use | Tylenol | 6500.0 mg |
| Liposomal Bupivacaine | Total Post-surgical Analgesic Medication Use | Ibuprofen | 4800.0 mg |
| Liposomal Bupivacaine | Total Post-surgical Analgesic Medication Use | Tylenol | 6500.0 mg |
Comparison: Standard Bupivacaine study arm compared to Liposomal Bupivacaine study arm for Ibuprofen usep-value: 0.248Wilcoxon (Mann-Whitney)
Comparison: Standard Bupivacaine study arm compared to Liposomal Bupivacaine study arm for Tylenol usep-value: 1Wilcoxon (Mann-Whitney)
Primary
Total Post-surgical Opioid Medication Use
Participants post-surgical analgesic medication use of IV hydrocodone and oxycodone measured in morphine equivalents (ME)
Time frame: First 72 hours following surgery completion
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Standard Bupivacaine | Total Post-surgical Opioid Medication Use | Hydrocodone | 0 Morphine Equivalents (ME) |
| Standard Bupivacaine | Total Post-surgical Opioid Medication Use | Oxycodone | 30.0 Morphine Equivalents (ME) |
| Liposomal Bupivacaine | Total Post-surgical Opioid Medication Use | Hydrocodone | 0 Morphine Equivalents (ME) |
| Liposomal Bupivacaine | Total Post-surgical Opioid Medication Use | Oxycodone | 30.0 Morphine Equivalents (ME) |
Comparison: Standard Bupivacaine study arm compared to Liposomal Bupivacaine study arm for Hydrocodone usep-value: 1Wilcoxon (Mann-Whitney)
Comparison: Standard Bupivacaine study arm compared to Liposomal Bupivacaine study arm for Oxycodone usep-value: 0.01Wilcoxon (Mann-Whitney)
Secondary
Emesis at 24, 48, and 72 Hours Post-surgery Completion
Number of times the patient vomited
Time frame: 24, 48, and 72 hours post-surgery
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Standard Bupivacaine | Emesis at 24, 48, and 72 Hours Post-surgery Completion | 24 hours post-surgery | 0.0 events |
| Standard Bupivacaine | Emesis at 24, 48, and 72 Hours Post-surgery Completion | 48 hours post-surgery | 0.0 events |
| Standard Bupivacaine | Emesis at 24, 48, and 72 Hours Post-surgery Completion | 72 hours post-surgery | 0.0 events |
| Liposomal Bupivacaine | Emesis at 24, 48, and 72 Hours Post-surgery Completion | 24 hours post-surgery | 0.0 events |
| Liposomal Bupivacaine | Emesis at 24, 48, and 72 Hours Post-surgery Completion | 48 hours post-surgery | 0.0 events |
| Liposomal Bupivacaine | Emesis at 24, 48, and 72 Hours Post-surgery Completion | 72 hours post-surgery | 0.0 events |
Comparison: Standard Bupivacaine study arm compared to Liposomal Bupivacaine study arm at 24 hours post-surgeryp-value: 0.957Wilcoxon (Mann-Whitney)
Comparison: Standard Bupivacaine study arm compared to Liposomal Bupivacaine study arm at 48 hours post-surgeryp-value: 0.353Wilcoxon (Mann-Whitney)
Comparison: Standard Bupivacaine study arm compared to Liposomal Bupivacaine study arm at 72 hours post-surgeryp-value: 0.165Wilcoxon (Mann-Whitney)
Secondary
Mean PACU Visual Analog Scale (VAS) (0-10) Pain Score
Scale Ranges from 0 (no pain) to 10 (extreme pain)
Time frame: Assessed while patient in PACU for recovery post-surgery per standard procedure
Population: Data not collected or analyzed
Secondary
Nausea at 24, 48, and 72 Hours Post-surgery Completion
Number of times patient reported feeling nauseous
Time frame: 24, 48, and 72 hours post-surgery
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Standard Bupivacaine | Nausea at 24, 48, and 72 Hours Post-surgery Completion | 24 hours post-surgery | 0.0 events |
| Standard Bupivacaine | Nausea at 24, 48, and 72 Hours Post-surgery Completion | 48 hours post-surgery | 0.0 events |
| Standard Bupivacaine | Nausea at 24, 48, and 72 Hours Post-surgery Completion | 72 hours post-surgery | 0.0 events |
| Liposomal Bupivacaine | Nausea at 24, 48, and 72 Hours Post-surgery Completion | 24 hours post-surgery | 0.0 events |
| Liposomal Bupivacaine | Nausea at 24, 48, and 72 Hours Post-surgery Completion | 48 hours post-surgery | 0.0 events |
| Liposomal Bupivacaine | Nausea at 24, 48, and 72 Hours Post-surgery Completion | 72 hours post-surgery | 0.0 events |
Comparison: Standard Bupivacaine study arm compared to Liposomal Bupivacaine arm at 24 hours post-surgeryp-value: 0.264Wilcoxon (Mann-Whitney)
Comparison: Standard Bupivacaine study arm compared to Liposomal Bupivacaine arm at 48 hours post-surgeryp-value: 0.97Wilcoxon (Mann-Whitney)
Comparison: Standard Bupivacaine study arm compared to Liposomal Bupivacaine arm at 72 hours post-surgeryp-value: 0.536Wilcoxon (Mann-Whitney)
Secondary
Patient Satisfaction With Pain Management at 72 Hours and 7-10 Days Post Surgery
Assessed on 0-10 scale (0 being worst level of satisfaction, 10 being best level)
Time frame: 72 hours and 7-10 days post surgery
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Standard Bupivacaine | Patient Satisfaction With Pain Management at 72 Hours and 7-10 Days Post Surgery | 72 hours post-surgery | 10.0 score on a scale |
| Standard Bupivacaine | Patient Satisfaction With Pain Management at 72 Hours and 7-10 Days Post Surgery | 7-10 days post-surgery | 10.00 score on a scale |
| Liposomal Bupivacaine | Patient Satisfaction With Pain Management at 72 Hours and 7-10 Days Post Surgery | 72 hours post-surgery | 9.5 score on a scale |
| Liposomal Bupivacaine | Patient Satisfaction With Pain Management at 72 Hours and 7-10 Days Post Surgery | 7-10 days post-surgery | 9.0 score on a scale |
Comparison: Standard Bupivacaine study arm compared to Liposomal Bupivacaine study arm at 72 hours post-surgeryp-value: 0.802Wilcoxon (Mann-Whitney)
Comparison: Standard Bupivacaine study arm compared to Liposomal Bupivacaine study arm at 7-10 days post-surgeryp-value: 0.656Wilcoxon (Mann-Whitney)
Secondary
Urinary Retention
Number of patients who had post-void residual (PVR) \>150cc's at voiding trial prior to discharge
Time frame: At voiding trial prior to discharge from hospital, approximately 72 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Bupivacaine | Urinary Retention | 1 Participants |
| Liposomal Bupivacaine | Urinary Retention | 1 Participants |
Secondary
VAS Pain Score at 24, 48, and 72 Hours Post-surgery Completion
Scale Ranges from 0 (no pain) to 10 (extreme pain)
Time frame: 24, 48, and 72 hours post-surgery completion
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Standard Bupivacaine | VAS Pain Score at 24, 48, and 72 Hours Post-surgery Completion | 24 hours post-surgery | 3.1 score on a scale |
| Standard Bupivacaine | VAS Pain Score at 24, 48, and 72 Hours Post-surgery Completion | 48 hours post-surgery | 2.5 score on a scale |
| Standard Bupivacaine | VAS Pain Score at 24, 48, and 72 Hours Post-surgery Completion | 72 hours post-surgery | 1.6 score on a scale |
| Liposomal Bupivacaine | VAS Pain Score at 24, 48, and 72 Hours Post-surgery Completion | 24 hours post-surgery | 3.5 score on a scale |
| Liposomal Bupivacaine | VAS Pain Score at 24, 48, and 72 Hours Post-surgery Completion | 48 hours post-surgery | 3.6 score on a scale |
| Liposomal Bupivacaine | VAS Pain Score at 24, 48, and 72 Hours Post-surgery Completion | 72 hours post-surgery | 2.4 score on a scale |
Comparison: Standard Bupivacaine study arm compared to Liposomal Bupivacaine study arm 24 hours post-surgeryp-value: 0.846Wilcoxon (Mann-Whitney)
Comparison: Standard Bupivacaine study arm compared to Liposomal Bupivacaine study arm 48 hours post-surgeryp-value: 0.49Wilcoxon (Mann-Whitney)
Comparison: Standard Bupivacaine study arm compared to Liposomal Bupivacaine study arm 72 hours post-surgeryp-value: 0.564Wilcoxon (Mann-Whitney)