Exparel Use for Popliteal Nerve Block in Postoperative Pain Control; After Ankle Fracture Fixation or Ankle Fusion Surgery: a Case Series

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.