EXPAREL for Minimally Invasive Supracervical Hysterectomies

Exparel is a local analgesic that utilizes bupivacaine in combination with the proven product delivery platform, DepoFoam®. Exparel (bupivacaine liposome injectable suspension) is a liposome injection of bupivacaine, an amide-type local anesthetic, indicated (bupivacaine liposome injectable suspension) for administration into the surgical site to produce postsurgical analgesia. Liposomal drug- containing formulations can provide for controlled drug release over an extended period of time.

The overall length of hospital stay (LOS) for patients undergoing laparoscopic (robot- assisted or traditional laparoscopy) supracervical hysterectomy varies widely in published reports; typical durations range between 0 days and 4 days.

That is because in recent years there has been a trend toward use of enhanced or "fast- track" discharge protocols to reduce LOS in patients undergoing this procedure, predicated primarily on reducing the time to achieve tolerance of oral liquid/food intake and improved GI function. Most patients experience moderate to extreme pain after surgery and effective postsurgical pain management is a key factor affecting patient recovery. Multimodal analgesia techniques involving analgesics, such as local anesthetics, oral or parenteral nonsteroidal anti-inflammatory medications, and oral or parenteral opioids, are recommended as the safest and effective approach to postsurgical pain control. Local anesthetics administered during surgery are frequently used as part of multimodal analgesic regimens; however, the duration of analgesia with these agents is short (12 hours). Bupivacaine has a long history of use in the surgical setting, and the efficacy of bupivacaine HCl administered perioperatively via wound infiltration or acute postsurgical pain is well established. A novel formulation of bupivacaine, ie, liposome bupivacaine (Pacira Pharmaceuticals, Inc., Parsippany, NJ), has been developed to address the need for longer-acting local anesthetics that can be administered as a single dose. The question becomes whether this drug is effective for postsurgical analgesia if given preoperatively via the intracervical stroma during minimally invasive gynecologic surgical procedures, specifically laparoscopic (robot--assisted or traditional laparoscopy) supracervical hysterectomy.

Paracervical/intracervical injections are used for cervical/uterine manipulation in various obstetrical and gynecological procedures. Lukas et al used the intracervical/paracervical block prior to hysteroscopic polypectomy, with good pain scores following the procedure and no serious adverse effects were noted. In addition, Chauan et al also noted good pain control with intracervical injection with lidocaine in patients undergoing a hysterosalpingography, which involves distended the uterus and injecting dye. Mankowshi et al also studied both intracervical and paracervical injections of lidocaine for first trimester suction curettage and found no difference between the two forms ensuring that both effective means of analgesia.

In the U.S., surgical site infections (SSI) affect 1 in 24 patients that undergo inpatient surgery. Most surgical site infection take place after day 5 , which will be out of the scope of timeframe for conduct of the survey. However a SSI can make the differentiation of pain from the surgery itself and pain from a complication of surgery difficulty to differentiate. The patient will be asked to specify where the pain is and ask if they have any associated vaginal discharge, foul smelling odor, and difficulty urinating and or passing a bowel movement. These responses will be tracked, and if the participant shows signs of a SSI, the patients may warrant a closer followup in the office and or asked to go directly to the Emergency Department (ED). The patients will still be included in the study but special note will be made of how many participant had SSI in the discussion portion.

Methods:

Randomized double blind placebo controlled pilot study. After IRB approval, 52 subjects will be consented to participate in the study. The study includes subjects undergoing minimally invasive (robot--assisted or traditional laparoscopy) supracervical hysterectomy under general anesthesia. This study will include women (35 - 75 years) who have American Congress of Obstetricians and Gynecologists (ACOG) and American Association of Gynecologic Laparoscopists (AAGL) physical classification status for a minimally invasive (robotic- assisted or traditional laparoscopy)supracervical hysterectomy.

Randomization will be done prior to recruitment of patient via computer software. There will be two groups with numbers 1-52, no numbers will be repeated. Each patient that is recruited will be assigned a number from 1-52 (in sequential order); the master list will be kept with the pharmacy director. Group A (control, n=26) to receive 20ml of saline while Group B (study, n=26) to receive 20ml of liposomal bupivacaine (EXPAREL) into the stroma of the cervix at the 4 and 8 o'clock positions (innervation insertion points of the cervix).

The MMC Pharmacy will prepare an individualized numbered bubble wrapped amber package accordingly to the randomization. It will be prepared prior to the recruitment and kept in the fridge in 4th floor PACU pharmacy. After the patient is consented and given a subject number, the package with the corresponding number will be picked up from the pharmacy and given to either the resident/attending (not involved in the study) who will share the contents of the package with the anesthesia team. While prepping, the same individual will inject the contents. The syringe will covered as to disguise the contents of the syringe.

The investigators will show a short video on how to prepare the Exparel as well the injection component in order to diminish the differences between the individuals.

Measurements:

The severity of pain will be assessed preoperatively in the holding area, PACU arrival, 12, 24, and 48 hours postoperatively using a numeric rating scale (NRS) at rest for pain with 0 = no pain and 10 = worst possible pain. Pain inquiries will assess low pelvic/suprapubic area and lower abdominal pain, type of pain (dull, achy, sharp, stabbing, etc.) and radiation of pain to a surrounding area. Other endpoints will include number of patients who required break through (additional) opioid analgesic medications, median time to first break through opioid use, total opioid analgesic requirement. The time, day and number of requests for break through (additional) analgesia will be noted by gynecologic surgery team (Resident or Fellow) participating in this study.

When the patient is home the patient will have a Pain Medication Diary that the investigators will provide for the patient prior to discharge. The patient will bring at the post-operative visit and or mail it in.