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

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.

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