Randomized Study of an Analgesic Device Enabling Local Anesthetic Delivery and Neuromodulation After Shoulder/Foot Surgery

Postoperative pain remains undertreated with inadequate analgesic options. Opioids have well-known limitations for both individuals and society; single-injection and continuous peripheral nerve blocks provide intense analgesia but are limited in duration to 24-72 hours; and current neuromodulation options-with a duration measured in weeks and not hours-are prohibitively expensive and require an additional procedure. One possible solution is a device currently under investigation to treat postoperative pain. The RELAY system (Gate Science, Moultonborough, New Hampshire) is comprised of a basic catheter-over-needle device to allow administration of a single-injection of local anesthetic via the needle (or catheter) followed by a perineural local anesthetic infusion via the remaining catheter (when desired). Subsequent to the local anesthetic administration, instead of removing the catheter as with all previous continuous peripheral nerve block equipment, electric current may be delivered via the same catheter and an integrated pulse generator for up to 28 days. This is potentially revolutionary because it would allow an anesthesiologist to deliver (1) a single-injection peripheral nerve block; (2) a continuous peripheral nerve block; and (3) neuromodulation using a single device that can theoretically be placed in the same amount of time required for a single-injection peripheral nerve block. Instead of providing fewer than 24 hours of postoperative analgesia, up to 28 days of pain control could be delivered without disruption of existing practice patterns. The ultimate objective of the proposed investigation is to investigate the post-operative analgesic potential of this investigational device and prepare for a pivotal multicenter clinical trial.

This feasibility study will be a series of participants all receiving both local anesthetic and electric current via a single device (RELAY, Gate Science, Moultonborough, New Hampshire). The purpose will be to optimize the insertion approach and stimulation administration during the first 7 days following foot and shoulder surgery as well as training the clinical investigators.

For individuals of childbearing potential, a sample of urine will be collected before any study interventions to confirm a non-pregnant state (this is standard procedure for all surgical patients). Participants will have standard external monitors placed and oxygen delivered by facemask or nasal cannula. The peripheral nerve block site(s) will be cleansed with chlorhexidine gluconate and isopropyl alcohol. Intravenous sedation/analgesia with midazolam and/or fentanyl will be titrated for patient comfort as is standard for peripheral nerve block administration. The nerves treated will include the sciatic proximal to the popliteal crease for foot surgery and the brachial plexus for shoulder surgery. The target nerve(s) will be visualized with ultrasound using a transverse cross-sectional (short axis) view and a skin wheal of local anesthetic will be raised inferior to the transducer to anesthetize the skin and then the track towards the target.

Participants will be randomly allocated to one of two possible treatments groups: (1) Neuromodulation or (2) Sham [Control]

Randomization will be stratified by anatomic location (shoulder and foot/ankle surgery) in a 1:1 ratio and in blocks of 2. Computer-generated randomization lists will be created by the UC San Diego Investigational Drug Service and participants allocated to the treatment groups in sequential order. Pulse generators are available that are capable of either (1) passing electrical current; or (2) not passing electrical current. Importantly, these 2 modes (active and sham) are indistinguishable in appearance, and therefore investigators, participants, and all clinical staff will be masked to treatment group assignment, with the only exception being the unmasked individuals who insert the RELAY and program the stimulator.

The RELAY system with the integrated needle will be inserted adjacent to the target nerve with an in-plane approach. Dextrose 5% in water (1-20 mL) will be injected via the needle to open a space around the target nerve(s), the catheter advanced, and the needle subsequently withdrawn.

Active treatment group. For participants randomized to active treatment, electrical current will be introduced with increasing intensity via the proximal and distal electrodes to optimize participant's perceived stimulation (control provided by the Gate Keeper app from an investigator's phone or tablet). Accurate lead placement will be confirmed with subject reports of comfortable sensations over the surgical site without eliciting muscle contractions. The minimum threshold and maximum comfortable amplitudes will be determined along with the optimal frequency, pulse duration, and anode/cathode. Starting from the lowest possible current the investigators increase the current until the participant states that they feel a "buzzing" sensation (some describe it as a "comfortable massage"). That is the minimal sensed current. The investigators will then continue increasing with the instructions to let them know when it starts to be less comfortable-and to stop us before it hurts. That is the maximum comfortable current. The stimulator will be then set to deliver the minimum threshold amplitude and turned off for surgery.

Sham treatment group. For participants receiving sham treatment, electric current will not reach the electrodes, but the investigators will connect to the RELAY to the mobile phone or tablet just as with the active group and set the parameters as follows: anode (distal), cathode (proximal), frequency (100 Hz), pulse duration (100 µs), and amplitude (5 mA).

Local anesthetic for active and sham groups. Local anesthetic (10 mL of lidocaine 2% with epinephrine) will be injected with negative aspiration every 3 mL and resulting sensory block confirmed to ensure accurate catheter tip placement. Following block confirmation (sensory deficits in the expected nerve distributions), the RELAY will be affixed with both surgical adhesive (2-Octyl 2-cyanoacrylate) at the entry site and a chlorohexidine-impregnated occlusive dressing. Subsequently, 10 mL of bupivacaine 0.5% with epinephrine will be injected negative aspiration every 3 mL along with a supplemental single-injection saphenous nerve block for foot/ankle surgery.

Intraoperatively, surgeons will be permitted to infiltrate the surgical area with long-acting local anesthetic as their common practice dictates.

Postoperatively, the stimulators will be connected to participants' phones and turned on.

If a patient's surgeon requests a postoperative continuous peripheral nerve block, a ropivacaine 0.2% infusion will be provided per standard UC San Diego protocol using 200 or 250 mL reservoirs for sciatic and brachial plexus infusions, respectively. This will provide an infusion lasting through postoperative day 1, and is approximately 1 day shorter than is our current standard-of-care.

After 7 days, participants in both the active and sham groups, themselves or their caretaker will remove the occlusive dressing and withdraw the catheter (and integrated electrodes) with gentle traction and rotation at home. The devices are single-use and disposable.

Following study completion, the results will be mailed electronically or by the United States Postal Service to all enrolled participants in written form using non-technical (e.g., "layperson") language.