Liposomal Bupivacaine in Vaginal Hysterectomy

Study Overview
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Brief Summary
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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
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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.

Official Title
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Preemptive Local Analgesia With Liposomal Bupivacaine in Vaginal Hysterectomy: A Randomized Controlled Study

Conditions
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Vaginal Hysterectomy

Intervention / Treatment
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* Drug: Liposomal bupivacaine
* Drug: Bupivacaine Hydrochloride


Participation Criteria
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Eligibility Criteria
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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 Known history of hepatic (liver) disease as evidenced by an AST or ALT that is greater than normal values Known history of renal (kidney) disease as evidenced by a serum creatinine that is greater than normal values Known history of prolonged QT (QTc greater than 500 m/s) 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 Allergy or contraindication to amide local anesthetics, celecoxib, ketorolac, NSAIDs, acetaminophen, gabapentin, sulfa drugs, or ondansetron Allergy to both oxycodone and hydromorphone Patients with acute gastrointestinal bleed that has occurred less than 6 months prior to study enrollment Adults lacking the ability to consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomized to receive either the bupivacaine HCl injection at the time of surgery or bupivacaine HCl plus liposomal bupivacaine.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard Bupivacaine<br>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. | Drug: Bupivacaine Hydrochloride<br>* 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.<br>|
| Experimental: Liposomal Bupivacaine<br>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 | Drug: Liposomal bupivacaine<br>* 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.<br>* Other names: Exparel;Drug: Bupivacaine Hydrochloride<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Post-surgical Opioid Medication Use | Participants post-surgical analgesic medication use of IV hydrocodone and oxycodone measured in morphine equivalents (ME) | First 72 hours following surgery completion | 
| Total Post-surgical Analgesic Medication Use | Participants post-surgical analgesic medication use of Ibuprofen and acetaminophen measured in milligrams (mg) | First 72 hours following surgery completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean PACU Visual Analog Scale (VAS) (0-10) Pain Score | Scale Ranges from 0 (no pain) to 10 (extreme pain) | Assessed while patient in PACU for recovery post-surgery per standard procedure | 
| VAS Pain Score at 24, 48, and 72 Hours Post-surgery Completion | Scale Ranges from 0 (no pain) to 10 (extreme pain) | 24, 48, and 72 hours post-surgery completion | 
| Nausea at 24, 48, and 72 Hours Post-surgery Completion | Number of times patient reported feeling nauseous | 24, 48, and 72 hours post-surgery | 
| Emesis at 24, 48, and 72 Hours Post-surgery Completion | Number of times the patient vomited | 24, 48, and 72 hours post-surgery | 
| Urinary Retention | Number of patients who had post-void residual (PVR) >150cc's at voiding trial prior to discharge | At voiding trial prior to discharge from hospital, approximately 72 hours | 
| 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) | 72 hours and 7-10 days post surgery |