Percutaneous Auricular Neuromodulation for Postoperative Analgesia

The proposed study will be a randomized, participant- and observer-masked, sham-controlled, parallel-arm, human participants pilot study with two primary aims:

Specific Aim 1: To determine the feasibility and optimize the protocol for a subsequent clinical trial that will compare the addition of percutaneous auricular neuromodulation to usual and customary analgesia following moderate-to-severely painful surgical procedures.

Specific Aim 2: To estimate the treatment effect of adding percutaneous auricular neuromodulation to usual and customary analgesia on pain and opioid consumption following various surgical procedures. This will provide an idea of the optimal surgical procedures amenable to this analgesic technique and allow determination of the required sample size of a subsequent definitive clinical trial.

Hypothesis 1: Auricular neuromodulation decreases pain in the 5 days following moderate-to-severely painful surgical procedures currently treated with a single-injection peripheral nerve block.

Hypothesis 2: Auricular neuromodulation decreases opioid use in the 5 days following moderate-to-severely painful surgical procedures currently treated with a single-injection peripheral nerve block.

This will be a single-center (UCSD), randomized, participant- and observer-masked, sham-controlled, parallel-arm human participants pilot study.

Enrollment. Participants will be consenting adults undergoing various surgical procedures usually resulting in moderate-to-severe postoperative pain and treated with single-injection peripheral nerve blocks. Study inclusion will be proposed to eligible patients prior to surgery. If a patient desires study participation, written, informed consent will be obtained using a current UCSD IRB-approved ICF. The study population of interest includes women and men of all races, ethnicity, sexual identity, and socioeconomic status.

Preoperative Procedures. Following written, informed consent, the investigators will record baseline anthropometric information (age, sex, height, weight, current pain level). Participants will have their single-injection peripheral nerve block administered using ropivacaine 0.5% with epinephrine (standard at the enrolling institution) prior to undergoing their surgical procedure per standard of care. A "successful" regional block will be defined as sensory- and motor-block onset in all expected nerve distributions within the 30 minutes following the local anesthetic injection. Participants with a successful regional block and undergo the anticipated surgical procedure will be randomized and continue within the study.

Treatment Group Assignment. Each participant will be randomized to one of two treatment groups: Active (Experimental) or Sham treatment. There are sham devices produced that are identical to active devices, only they do not deliver electrical current. Randomization will be stratified by surgical procedure, in block sizes of 2. The computer-generated randomization list will be created by the University of California San Diego Investigational Drug Service in a 1:1 treatment group ratio assigned only after successful peripheral nerve block administration and the participant underwent the anticipated surgical procedure. The active and sham stimulators are indistinguishable in appearance, and therefore investigators, participants, and all clinical staff other than the individual who opens the randomization envelope and chooses a sham or active device will be masked to treatment group assignment for the duration of the data collection period.

Study intervention. The NSS-2 Bridge device will be affixed to the ear and activated prior to discharge from the recovery room (Experimental). There is currently no consensus regarding the placement on the ipsilateral or contralateral ear relative to the surgical procedure (if sided). Therefore, the investigators will apply the device to the side that the participant sleeps on least, to optimize comfort in bed and sleep.

Postoperative course. In addition to the experimental device and single-injection peripheral nerve block, participants will receive standard-of-care oral and intravenous postoperative analgesics which can include acetaminophen, ibuprofen, ketorolac, and opioids (this is surgeon- and patient-dependent). Therefore, all patients of this study-regardless of the treatment arm they are randomized to-will continue to receive current usual and customary analgesia: all will receive the same combination of acetaminophen, ibuprofen, ketorolac, opioids, and a single-injection peripheral nerve block as they would regardless of study participation. Prior to discharge, participants and their caretakers will be provided with verbal instructions regarding the care of the stimulator, and the telephone and pager numbers of an investigator available at all times during the first 5 days of treatment. The instructions for the stimulator are few: (1) participants can shower, but use a shower cap to cover the stimulator; (2) there are no controls so there is nothing that needs to be adjusted; (3) the device will run out of power after 5 days; (4) the investigators will call participants every day to answer any questions participants might have and describe how to remove the device as that time approaches.

Participants will be discharged when ready, as determined by standard criteria by the masked surgical service. Participants will be discharged home with their NSS-2 Bridge in situ and a prescription for immediate-release oral opioid, preferably oxycodone 5 mg tablets, taken for breakthrough pain. Participants will be contacted by telephone for end point collection beginning on postoperative day 1. The NSS-2 Bridge devices will be removed by patients or their caretakers at home on postoperative day 5. Similar to perineural catheters, this procedure encompasses simply removing the small dressings (the electrodes remain adhered to the dressings and therefore do not require a separate extraction step), removing the stimulator from behind the ear with simple traction, and discarding all components (these are disposable, single-use devices).

At the conclusion of the study, participants will be informed of the main results in lay-person language by either email or the U.S. Postal Service.

Study outcomes: This is an exploratory pilot study to assist in planning a subsequent definitive trial and the investigators therefore have no data analysis plan. The investigators will enroll convenience samples for each of the surgical procedures of up to 30 participants for each procedure and anticipate analyzing some surgical procedure separately from the others (hips, knees, breast, hernia/cholecystectomy, septoplasty). The two primary outcomes will be (1) the mean of the "average" pain recorded on postoperative days 1-5 measured with the Numeric Rating Scale ("average" pain is included in the Brief Pain Inventory pain domain); and (2) the cumulative opioids consumed from recovery room discharge until postoperative day 5, as measured in oral oxycodone equivalents.