Exparel and Ankle Surgery
Condition: Ankle Fracture
MeSH terms: Ankle Fractures
Study type: Interventional

Summary: 
      This study involves a drug called Exparel that has been approved by the US Food and Drug
      Administration (FDA), for application directly to wound sites. EXPAREL® is a long acting pain
      reliever. It is being given in this study to see if it provides safe and effective pain
      relief after ankle surgery. Because it is a long acting drug, it may lessen pain relief for
      as much as 72 hours after surgery.

      EXPAREL® has not been approved by the FDA for administration by popliteal block, which is the
      method the study doctors will use to give the patients the drug. Giving the drug by popliteal
      block involves inserting a small tube in to the back of the knee to deliver the drug. The
      study doctors wish to determine if patients undergoing ankle surgery and receiving this drug
      have less pain and less need for narcotic medication.
    

Detailed description: 
      Managing postoperative pain remains a paramount topic in anesthesiology, since a significant
      amount of patients continue to report discomfort after their inpatient and outpatient
      surgeries. Orthopedic lower limb surgeries are known to induce prolonged pain after the
      procedure requiring the increased use of multi-modal analgesia. Popliteal fossa nerve block
      targeting the sciatic nerve has been utilized to effectively control postoperative pain and
      to lower opioid requirements for patients undergoing foot and ankle surgeries.The sciatic
      nerve divides into its tibial and common fibula branches approximately 4 to 13 centimeters
      above the popliteal crease. The tibial nerve innervates the heel and the plantar aspect of
      the foot, while the common fibula nerve, also known as the common peroneal nerve, supplies
      the lateral aspect of the leg and the dorsum of the foot.

      Bupivacaine, a local anesthetic and analgesic, is currently used as an agent to address
      postsurgical analgesia. However, administering a large dose of bupivacaine for nerve blockade
      has been reported to lead to complications such as infection, hematoma, vascular puncture,
      toxicity and, even severe systemic side effects. EXPAREL® (multi-vesicular liposomal
      bupivacaine) is a multi-vesicular liposomal form (DepoFoam drug delivery systems) of
      encapsulated bupivacaine that allows for the slow diffusion of the drug over an extended
      period of time of 72 hours, versus the 8 hour duration of Bupivacaine Hydrogen Chloride
      (HCl). EXPAREL® has been shown to provide successful prolonged analgesia after wound
      infiltration during several surgical procedures.In addition to the long lasting pain relief,
      studies also highlight the improved clinical outcomes of patients and lower economic costs
      associated with liposomal bupivacaine when compared to bupivacaine Hydrogen chloride.
      However, studies evaluating the use of EXPAREL® for nerve blocks are limited. Richard et. al.
      demonstrated the safety of EXPAREL® to Bupivacaine and saline on the brachial plexus of dogs
      and rabbits revealing no irritation or tissue damage even at high doses. Furthermore, after
      administering liposomal bupivacaine via single epidural injections into humans, Viscussi et.
      al. reported longer sensory blockade and shorter motor blockade compared to bupivacaine HCl,
      enabling quicker recovery and mobility for the patient.

      The primary objectives of this study is to (1) evaluate the efficacy of the study drug
      EXPAREL® with respect to the safety and duration of the postoperative analgesic effect on
      five subjects following single dose injection via a popliteal nerve block. Based on the data
      analysis from this case series, a decision will be made as to whether a large randomized,
      double-blinded, prospective study is warranted.

      Methods and Materials The purpose of the popliteal nerve block with the use of EXPAREL® will
      be explained to the potential subject. Demographic information will be obtained including
      age, gender, past medical history, past surgical history, hospitalizations, current
      medications, allergies, and history of drug and alcohol abuse. Preoperative baseline pain
      score, motor strength and sensation will be documented by a study team member, prior to
      carrying out study procedures. The Visual Acuity Scale (VAS) will be explained to the
      patient. A Semmes Weinstein monofilament exam with a size 5.07 monofilament will be performed
      to rule out any occult nerve injury.

      On the day of surgery all eligible subjects will receive a single dose of study drug EXPAREL®
      1.3% 20 ml (266mg) will be administered within 1 hour prior to the surgical procedure as a
      popliteal nerve block. This block will be done by a trained anesthesiologist, using an
      ultrasound-guided technique (Mindray model # M-7). Prior to induction of anesthesia, standard
      monitoring devices such as non-invasive blood pressure, EKG and pulse oximetry for oxygen
      saturation will be started. Bispectral Index (BIS) will be maintained in a range of 30-60.
      Continuous vital sign monitoring will be done intraoperatively. All patients will be
      administered midazolam 0.5 mg to 4 mg/kg to achieve anxiolysis. Induction of anesthesia will
      also include Lidocaine 1.5mg/kg, Propofol 1.5-3 mg/kg, Fentanyl 1-2mcg/kg. If indicated the
      muscle relaxant of the anesthesiologists choice: either Succinylcholine 1.5 mg/kg, Rocuronium
      0.6mg/kg or Nimbex 0.2mg/kg to titrate Train of Four (TOF) at 1-2 twitches until 30 minutes
      prior to the end of the surgical procedure. Anesthestic maintenance with 0.8 to 1.5 Minimum
      Alveolar Concentration (MAC) of sevoflurane as indicated by end tidal concentration in oxygen
      and air mixture of 50% each and fraction of inspired oxygen ( FiO2) may be increased if
      oxygen saturation is less than 96%. The use of fentanyl will be permitted during surgery.
      However, intraoperative administration of any other narcotics or analgesics (including
      intrathecal opioids), local anesthetics, or anti-inflammatory agents is prohibited, unless
      needed to treat an adverse even (AE). The amount of fentanyl used will be recorded.
      Ondansetron0.1mg/kg will be used as an antiemetic prior to reversal of muscle relaxant with
      neostigmine and glycopyrrolate.

      Upon extubation, the patient will be transferred to the post-anesthesia care unit (PACU). At
      this time quality of the regional block will be assessed. Motor strength will be rated as
      follows: 2=no voluntary movement, 1=some muscle weakness and 0=no muscle weakness. The
      sensory block (cold test) will be evaluated by the following criteria: 2=no sensation,
      1=decreased sensation and 0=normal sensation. All blocks rated as 0 for both sensory and
      motor testing, will be considered failed blocks and will be excluded from the data collection
      for the remainder of the study.

      All subjects will receive rescue medication upon request for pain control whether they remain
      in the data collection or not. Patients will be treated with intravenous Hydromorphone 0.5mg
      for a pain score ≥ 4 out of 10 on the VAS scale for a maximum of 2 divided doses. Vital signs
      (heart rate, blood pressure, respiratory rate and pulse oxymetry) will be continuously
      monitored in the Post Anesthesia Care Unit (PACU) and recorded as to the standard protocol
      that is every 5 minutes for the first 15 minutes, 15 minute intervals for the next hour and
      then every 30 minutes until discharge. Pain score and sedation scores will be obtained using
      the VAS and Ramsay sedation scale, respectively. All pain scores will be assessed with
      patient in the resting position. No patient will be discharged from the PACU with a VAS >than
      4 out of 10. If this cannot be achieved with the rescue medication indicated above the
      patient will be started on Patient Controlled Analgesia (PCA). PCA orders are as follows
      Hydromorphone 0.02mg every 6 minutes, no basal rate, and no four-hour maximum. Neurological
      and sensory assessment will be assessed on arrival, at 60 minutes and at 120 minutes. Those
      parameters assessed will include numbness of tongue, lips and mouth, metallic taste, problems
      with hearing or vision, muscle twitching and does the subject feel cold in the innervated
      dermatomes.

      Time to discharge readiness from PACU will be documented. After PACU discharge oxycodone
      5mg/325mg acetaminophen 1 or 2 tablets every 6 hours will be offered for breakthrough pain.
      The doses and timing of all pain medications will be recorded while hospitalized and the
      subject's will be provided a diary to record pain and medication taken at home. The research
      coordinator will follow-up with the patients on post-operative days for those who have been
      discharged to home, in order to ensure that questionnaires and diaries are completed.

      On POD 1, POD 2 and POD 3, a pain questionnaire will be completed addressing the quality of
      postoperative pain relief, pain scale, and incidence and severity of any side effects,
      including palpitations, nausea, vomiting as well as burning, numbness, tingling, and rebound
      pain. Peripheral neuropathy sequelae will be assessed subjectively via the questionnaire. The
      subject will also be evaluated for amount of pain medication required and any opioid side
      effects will be documented. On POD 3 the subject will be asked to provide an overall opinion
      of the pain control using a 5-point Likert scale.
    

Intervention name(s): Exparel
Intervention type(s): Drug
Other intervention name(s): liposomal bupivacaine
Intervention MeSH terms: Bupivacaine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment