Prospective Randomized Trial of Penile Nerve Block With Liposomal Bupivacaine for Hypospadias Repair vs Standard Penile Block With Bupivacaine

Male patients who are greater than 6 months of age will be enrolled in the study prior to elective outpatient hypospadias repair with ASA class 1-2. For a male who meets the inclusion criteria, after informed consent is obtained, he will be randomized at a 1:1 basis to standard penile block with bupivacaine or penile block with liposomal bupivacaine. All patients will be pre-medicated per standard practice with 0.1-0.2 mg PO hydrocodone and 0.25-0.35 mg PO versed.

• Control patients will receive a standardized amount of 0.25% bupivacaine based on age-based ideal body weight calculated as follows: 6 months to 1 year old, 2.5 mg/kg; >1-year-old, 3 mg/kg. Calculating volume of agent that can be administered in mL = allowable ideal body weight dose (mg/kg) x (weight in kg) x (1/ concentration of local anesthetic agent). For example, the average 9-month old male is around 9 kg, therefore, they will receive 9 mL of 0.25% bupivacaine (2.5 mg/mL).
• Treatment patients will receive Liposomal Bupivacaine (Exparel) 1.3% (266mg/20mL or 133mg/10mL) based on current PK studies for the agent. A dose of 4mg/kg will be used. For example, using the fact that the average 9-month old is around 9kg the patient would receive 2.7 mL of liposomal bupivacaine. Since the liposomal bupivacaine has a delayed onset of action, the patients in this arm would receive 0.25% bupivacaine for the immediate analgesic needed for the operative procedure. According to the prescribing information for Pacira pharmaceuticals, bupivacaine HCl can be administered immediately before or in the same syringe as liposomal bupivacaine (Exparel). This is only true as long as the ratio of bupivacaine HCl to Liposomal bupivacaine (Experal) dose does not exceed 1:2 ratio of the agents. Also, a 10mL vial of liposomal bupivacaine (Experal) contains 133mg of free base bupivacaine, which is the molar equivalent of 150mg of bupivacaine HCl. (reference Pacira prescribing information) Therefore, if the dose of 2.7ml of liposomal bupivacaine is used for a 9kg child, then the patient is allowed up to 18mg of bupivacaine HCl to be mixed with the liposomal bupivacaine (1:2 ration or 50% rule from Pacira prescribing information). Our patients will receive a 0.25% bupivacaine dosage that will be calculated using the ideal body weight calculation as stated above, but instead of using 2.5mg/kg dosage it would need to be 2mg/kg so the 50% ratio is met to fit the pharmacodynamics of using liposomal bupivacaine in a safe and predictable manner. Therefore, for the 9kg patient, he would receive 2.7 mL of liposomal bupivacaine and 7.2 mL of 0.25% bupivacaine for a total volume of 9.9 mL of total volume.
• Using the 0.25% bupivacaine in the control arm and experimental arm allows the volume of the local anesthetic to be close in-between the cohorts and ideal for giving a complete penile ring block, since the volume of liposomal bupivacaine needed is very small. The use of 0.25% bupivacaine is important in the liposomal bupivacaine arm, because the liposomal bupivacaine has a delayed release and could not offer local anesthesia until closer to 45 minutes after application. This could potentially lead to patients requiring more systemic anesthesia if liposomal bupivacaine is used alone. Therefore, like many other pediatric providers using liposomal bupivacaine, it will be given in conjunction with 0.25% bupivacaine to improve immediate local anesthesia.
• To standardize the technique of the blocks, each block will be given in the same fashion by each of the pediatric urology providers.

1. Enrollment and Consenting:

• Patients that fit the inclusion criteria will have the trial discussed with them in the preoperative consultation room with the attending urologist. If the patients' consent to being enrolled, they will receive a copy of the Face, Legs, Activities, Cry, Consolability (FLACC) scale, the post procedure log sheet for the study to record the FLACC scores and PRN medication doses and indication for PRN medication administration, and they will also be shown a video on how to use the FLACC scoring system.
• One of the concerns for using the FLACC as an outcome measure of postoperative pain and a measure of how effective liposomal bupivacaine is in comparison to bupivacaine alone, is the intra-operator differences among patients' parents and reporting a score. We are attempting to control for this by showing a video with an example patient and scoring of this patient for each family to view. This video will be available to enrolled families via email so they can show it to other family members or caregivers (potentially grandparents or nanny/babysitters) who may be scoring the child in the post-operative period, but were not present on the day of surgery, or during the preoperative consultation.

Day of Surgery

• The parent/LAR will most likely be approached for consenting at the preoperative consultation, but will be given ample time to consider, and we will verify they continue to desire to participate on the day of their surgery by the research fellow.
• After the patient is enrolled, the research fellow will pull the next envelope to determine which group each patient will be assigned to.
• The anesthesia team will receive the treatment arm assignment 0.25% bupivacaine HCl alone vs. 0.25% bupivacaine and 1.3% liposomal bupivacaine from the research team member. And enter the order for local anesthetic agent in Epic that will be used during the surgery for the penile block with the appropriate patient weight.
• The agent will be processed by pharmacy and dispensed to the OR for the urologist to administer as a penile ring block at the induction of anesthesia. The urologist and anesthesiologist will be aware of the agent given to the patient for safety concerns, but this should not interfere with trial endpoints since scores will be awarded by the parents who are blinded to the anesthetic agent used.
• The block will be administered in a standard fashion (ring block) by the pediatric urologist in either arm of the study.