EXPAREL for Minimally Invasive Supracervical Hysterectomies
Condition: Pain
Study type: Interventional
Phase: Phase 4

Summary: 
      The aim of the of the study is a reduction in minimally invasive supracervical hysterectomy
      postsurgical pain, which may result in less need for supplemental opioid pain medications,
      fewer opioid related adverse events, and a better recovery experience for patients, which may
      offer an economic benefit to health care systems.

      Intracervical preoperative dose of Exparel during minimally invasive (robotic--assisted or
      traditional laparoscopy) supracervical hysterectomy reduces cumulative pain scores for up to
      24 hours and reduces overall requests for break through (additional) analgesia with opioid
      consumption compared with placebo.
    

Detailed description: 
      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.
    

Intervention name(s): Saline Solution for Injection; Exparel
Intervention type(s): Drug; Drug
Intervention description(s): Injection of 20mL of 0.9%Normal Saline; 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.
Other intervention name(s): Standard; liposomal bupivicaine
Intervention MeSH terms: Bupivacaine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: laparoscopy; supracervical hysterectomy; Multimodal pain management; bupivacaine liposome; Exparel