Randomized Trial of Wound Infiltration With Extended-release Bupivacaine Before Laparoscopic or Robotic Hysterectomy

Phase 4

Completed

Conditions: Pain, Postoperative
Surgical Procedure, Unspecified

Interventions: Drug: Bupivacaine HCl
Drug: Liposomal Bupivacaine

Registration Number: NCT02352922

Lead Sponsor: AdventHealth

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 64

Inclusion Criteria

Benign indication for surgery
Planned multiport laparoscopic or robotic assisted hysterectomy
Non-pregnant
Able to provide informed consent
Owns smartphone or computer with internet access
Willing to provide contact phone number and accept SMS text messages
Ability to speak and read English (because texts and online surveys will be in English only)

Exclusion Criteria

Planned additional procedures (e.g. incontinence surgery, prolapse repair or bowel surgery)
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
History of substance or alcohol abuse within the past 2 years

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bupivacaine HCl	Bupivacaine HCl	short-acting bupivacaine
Liposomal Bupivacaine	Liposomal Bupivacaine	extended-release bupivacaine (EXPAREL)

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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 Post-op Day 14	Post-Operative Day 14	Pain scale (0-10), 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
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
Number of Participants With Adverse Events	Post-Operative Day 14
NRS Pain Score at 16 Hours	16 hours post-op	Pain scale (0-10), where 0 = no pain and 10 = worst pain imaginable
Total Opioid Use End of Post-op Day 3	72 hrs post-op	Total use of home opioids by pill count/ oral morphine equivalents
NRS Pain Score Post-op Day 2	2 days post-op	Pain scale (0-10), where 0 = no pain and 10 = worst pain imaginable
Quality of Life as Measured by the Brief Pain Inventory (BPI)	Post-Operative Day 14	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
Total Opioid Use Prior to Hospital Discharge	24 hours	Oral morphine equivalent of opioid use while in the hospital
Total Opioid Use at Post-op Day 14	Post-Operative Day 14	Total use of home opioids by pill count/ oral morphine equivalents