Pain mechanisms in the transgender individual: a review.

Specific Aim: Provide an overview of the literature addressing major areas pertinent to pain in transgender persons and to identify areas of primary relevance for future research. Methods: A team of scholars that have previously published on different areas of related research met periodically though zoom conferencing between April 2021 and February 2023 to discuss relevant literature with the goal of providing an overview on the incidence, phenotype, and mechanisms of pain in transgender patients. Review sections were written after gathering information from systematic literature searches of published or publicly available electronic literature to be compiled for publication as part of a topical series on gender and pain in the Frontiers in Pain Research. Results: While transgender individuals represent a significant and increasingly visible component of the population, many researchers and clinicians are not well informed about the diversity in gender identity, physiology, hormonal status, and gender-affirming medical procedures utilized by transgender and other gender diverse patients. Transgender and cisgender people present with many of the same medical concerns, but research and treatment of these medical needs must reflect an appreciation of how differences in sex, gender, gender-affirming medical procedures, and minoritized status impact pain. Conclusions: While significant advances have occurred in our appreciation of pain, the review indicates the need to support more targeted research on treatment and prevention of pain in transgender individuals. This is particularly relevant both for gender-affirming medical interventions and related medical care. Of particular importance is the need for large long-term follow-up studies to ascertain best practices for such procedures. A multi-disciplinary approach with personalized interventions is of particular importance to move forward.

An Interdisciplinary, Comprehensive Recovery Pathway Improves Microsurgical Breast Reconstruction Delivery.

INTRODUCTION: Free-flap (autologous) breast reconstruction demonstrates superiority over alloplastic approaches but is offered infrequently. Enhanced recovery protocols can address postoperative challenges, but most literature is limited to inpatient interventions and outcomes. This study describes an adoptable, longitudinally comprehensive and multidisciplinary recovery pathway for autologous reconstruction which adds to the current guidelines. The authors aimed to allow perioperative outcomes comparable to alloplastic reconstructions. METHODS: All autologous Comprehensive Recovery Pathway (CRP) subjects from a single surgeon were retrospectively included. A comparator group of equal size was randomly selected from institutional subpectoral and dual-plane tissue expander patients having Enhanced Recovery After Surgery guideline-directed care. All subjects in both cohorts received preoperative paravertebral regional blocks. Operative detail, inpatient recovery, longitudinal morphine equivalents (MEs) required, and complications were compared. RESULTS: Each cohort included 71 cases (99 breasts). Despite longer operations, intraoperative MEs were fewer in autologous cases ( P = 0.02). Morphine equivalents during inpatient stay were similar between cohorts, with both being discharged on median day 2. Multivariate regression demonstrated a 0.8-day increased stay for autologous subjects with additional contribution from bilateral cases, body mass index, and age ( P < 0.05). Autologous subjects were regularly discharged postoperative day 1 (17%) and postoperative day 2 (39%), with trend toward earlier discharge ( P < 0.01). Outpatient MEs were significantly fewer in autologous subjects, corresponding to a 30- to 150-mg oxycodone difference ( P < 0.01). Major complication occurred in 12.7% of autologous and 22.5% of alloplastic subjects ( P = 0.11). Flap loss occurred in 1 autologous subject versus 11 alloplastic failures ( P < 0.01). CONCLUSIONS: This study details partnership between the plastic surgery service, regional and acute pain anesthesia services, and dedicated nursing with longitudinal optimizations allowing perioperative outcomes improved over current literature. Patients in the CRP used fewer opioids from operation through follow-up with comparable length of stay and significantly fewer reconstructive failures than alloplastic subjects. The pathway may be quickly adopted into academic practice patterns and mitigates traditional barriers, allowing extension of autologous reconstruction offerings.

Subcutaneous Oxytocin Injection Reduces Heat Pain: A Randomized-Controlled Trial.

Oxytocin (OT) is a neuropeptide broadly implicated in social relationships and behavior. OT also exerts antinociceptive and pain-reducing effects in both humans and rodents. Recent research in rodents demonstrates that these effects can be peripheral and local. In human studies, intravenous OT has reduced visceral pain, and subcutaneous injection of OT has reduced postsurgical pain. However, the local effects of subcutaneous OT on experimental pain have not been studied. We conducted a 2-session crossover study during which healthy adults received a subcutaneous injection of synthetic OT (4 mcg/2 mL) or saline placebo (isotonic saline 2 mL), in a randomized and double-blinded manner. Eighteen participants completed full study procedures. We hypothesized that 10 minutes after injection, OT would reduce measures of acute mechanical pain, pressure pain, and heat pain perception. Subcutaneous OT significantly reduced ratings of heat pain intensity and unpleasantness (both P < .01), but did not alter mechanical pain, pressure pain, or heat pain threshold (all P > .05). Changes in heat pain were observed only on the injected arm and not on the contralateral arm, confirming a localized mechanism. These findings confirm the ability of OT in or near the skin to modulate nociceptive processes in cutaneous tissues in human adults, opening exciting avenues for further mechanistic research as well as potential clinical applications for acute pain. PERSPECTIVE: This randomized-controlled trial showed that a subcutaneous injection of OT could reduce perception of heat pain tested with a thermode. OT did not alter mechanical or pressure pain or thresholds for perceiving heat pain. These findings are relevant to scientists and clinicians seeking nonaddictive local drug treatments for pain.

Robot-assisted laparoscopic nephrectomy: early outcome measures with the implementation of multimodal analgesia and intrathecal morphine via the acute pain service.

PURPOSE: The objective of this study was to perform a retrospective cohort analysis, in which we measured the association of an acute pain service (APS)-driven multimodal analgesia protocol that included preoperative intrathecal morphine (ITM) compared to historic controls (i.e., surgeon-driven analgesia protocol without ITM) with postoperative opioid use. METHODS: This was a retrospective cohort study in which the primary objective was to determine whether there was a decrease in median 24-h opioid consumption (intravenous morphine equivalents [MEQ]) among robotic nephrectomy patients whose pain was managed by the surgical team prior to the APS, versus pain managed by APS. Secondary outcomes included opioid consumption during the 24-48 h and 48-72 h period and hospital length of stay. To create matched cohorts, we performed 1:1 (APS:non-APS) propensity score matching. Due to the cohorts occurring at the different time periods, we performed a segmented regression analysis of an interrupted time series. RESULTS: There were 76 patients in the propensity-matched cohorts, in which 38 (50.0%) were in the APS cohort. The median difference in 24-h opioid consumption in the pre-APS versus APS cohort was 23.0 mg [95% CI 15.0, 31.0] (p < 0.0001), in favor of APS. There were no differences in the secondary outcomes. On segmented regression, there was a statistically significant drop in 24-h opioid consumption in the APS cohort versus pre-APS cohort (p = 0.005). CONCLUSIONS: The implementation of an APS-driven multimodal analgesia protocol with ITM demonstrated a beneficial association with postoperative 24-h opioid consumption following robot-assisted nephrectomy.

Percutaneous auricular neuromodulation (nerve stimulation) for the treatment of pain following cholecystectomy and hernia repair: a randomized, double-masked, sham-controlled pilot study.

BACKGROUND: Percutaneous auricular nerve stimulation (neuromodulation) involves implanting electrodes around the ear and administering an electric current. A device is currently available within the USA cleared to treat symptoms from opioid withdrawal, and multiple reports suggest a possible postoperative analgesic effect. The current randomized controlled pilot study was undertaken to (1) determine the feasibility and optimize the protocol for a subsequent definitive clinical trial; and (2) estimate the treatment effect of auricular neuromodulation on postoperative pain and opioid consumption following two ambulatory surgical procedures. METHODS: Within the recovery room following cholecystectomy or hernia repair, an auricular neuromodulation device (NSS-2 Bridge, Masimo, Irvine, California, USA) was applied. Participants were randomized to 5 days of either electrical stimulation or sham in a double-blinded fashion. RESULTS: In the first 5 days, the median (IQR) pain level for active stimulation (n=15) was 0.6 (0.3-2.4) vs 2.6 (1.1-3.7) for the sham group (n=15) (p=0.041). Concurrently, the median oxycodone use for the active stimulation group was 0 mg (0-1), compared with 0 mg (0-3) for the sham group (p=0.524). Regarding the highest pain level experienced over the entire 8-day study period, only one participant (7%) who received active stimulation experienced severe pain, versus seven (47%) in those given sham (p=0.031). CONCLUSIONS: Percutaneous auricular neuromodulation reduced pain scores but not opioid requirements during the initial week after cholecystectomy and hernia repair. Given the ease of application as well as a lack of systemic side effects and reported complications, a definitive clinical trial appears warranted. TRIAL REGISTRATION NUMBER: NCT05521516.

Percutaneous auricular neuromodulation (nerve stimulation) for the treatment of pain following total knee arthroplasty: a randomized, double-masked, sham-controlled pilot study.

BACKGROUND: Percutaneous auricular nerve stimulation (neuromodulation) is an analgesic technique involving the percutaneous implantation of multiple leads at various points on/around the ear followed by the delivery of electric current using an external pulse generator. A device is currently available within the USA cleared to treat symptoms from opioid withdrawal, and multiple reports suggest a possible postoperative analgesic effect. The current randomized, controlled pilot study was undertaken to (1) determine the feasibility and optimize the protocol for a subsequent definitive clinical trial and (2) estimate the treatment effect of auricular neuromodulation on postoperative pain and opioid consumption following total knee arthroplasty. METHODS: Within the recovery room following primary, unilateral, total knee arthroplasty, an auricular neuromodulation device (NSS-2 Bridge, Masimo, Irvine, California, USA) was applied using three percutaneous leads and one ground electrode. Participants were randomized to 5 days of either electrical stimulation or sham stimulation in a double-masked fashion. Participants were discharged with the stimulator in situ and removed the disposable devices at home. The dual primary treatment effect outcome measures were the cumulative opioid use (oral oxycodone) and the mean of the "average" daily pain measured with the Numeric Rating Scale for the first 5 postoperative days. RESULTS: During the first five postoperative days, oxycodone consumption in participants given active stimulation (n=15) was a median (IQR) of 4 mg (2-12) vs 13 mg (5-23) in patients given sham (n=15) treatment (p=0.039). During this same period, the average pain intensity in patients given active stimulation was a median (IQR) of 2.5 (1.5-3.3) vs 4.0 (3.6-4.8) in those given sham (p=0.014). Awakenings due to pain over all eight postoperative nights in participants given active stimulation was a median (IQR) of 5 (3-8) vs 11 (4-14) in those given sham (p<0.001). No device-related localized cutaneous irritation, systemic side effects, or other adverse events were identified. CONCLUSIONS: Percutaneous auricular neuromodulation reduced pain scores and opioid requirements during the initial week after total knee arthroplasty. Given the ease of application as well as the lack of systemic side effects and reported complications, a definitive clinical trial appears warranted. TRIAL REGISTRATION NUMBER: NCT05521516.

Association of thoracic epidural analgesia and hospital length of stay for patients undergoing thoracotomy: a retrospective cohort analysis.

INTRODUCTION: Regional anesthesia has been shown to be efficacious for analgesia in patients who underwent thoracotomies. The objective of this study was to analyze the association of epidurals and peripheral regional anesthesia with time to hospital discharge for these patients. METHODS: This was a retrospective cohort study using National Surgical Quality Improvement Program dataset from 2014 to 2020. Propensity-matched cohorts were assembled based on use of regional anesthesia, peripheral regional anesthesia, or epidural. Fine-Gray competing risk regressions were used to explore the association between regional anesthesia use and rate of discharge. The subdistribution hazard ratio (HR) represented relative discharge rates, and in-hospital death was a competing event. A sensitivity analysis was subsequently performed in which patients with American Society of Anesthesiologists score ≥4 were removed. RESULTS: There were 4350 patients included in this analysis, in which 472 (10.8%) received a peripheral regional anesthesia nerve block and 565 (13.0%) received thoracic epidural analgesia. The subdistribution HR for rate of discharge in the epidural versus non-epidural cohort was 1.09 (95% CI 1.01 to 1.18), thus epidurals were associated with an increased rate of discharge over time. However, this benefit was no longer apparent with the sensitivity analysis. The subdistribution HR for rate of discharge in the peripheral regional anesthesia versus no regional anesthesia cohort was 1.26 (95% CI 1.15 to 1.39), thus peripheral regional anesthesia was associated with an increased rate of discharge over time. This benefit remained even with the sensitivity analysis. CONCLUSIONS: Thoracic epidural use when compared with no regional anesthesia was associated with decreased length of stay following thoracotomy in our primary analysis. The difference was no longer apparent with the sensitivity analysis. Peripheral regional anesthesia was associated with decreased length of stay even after sensitivity analysis.

Intrathecal Morphine Injection for Postoperative Analgesia Following Gender-Affirming Pelvic Surgery: A Retrospective Case-Control Study.

Background Gender-affirming pelvic surgery (GAPS) can be associated with significant postoperative pelvic pain. Given the lack of available peripheral nerve blocks to the perineum, intrathecal morphine (ITM) injection could offer a potent analgesic modality for this patient population. No prior studies to date have been performed examining the analgesic effects of intrathecal morphine for these patients. Methods This retrospective case-control study aims to understand the postoperative analgesic effects of intrathecal morphine for these patients with a historical comparison group of patients who did not receive intrathecal morphine. Results Fourteen patients presented for gender-affirming pelvic surgery over an eight-month period at a single institution and were offered intrathecal morphine for postoperative analgesia. Their analgesic results were compared to a similar historical group of 13 patients who were not offered or declined intrathecal morphine. Conclusions Intrathecal morphine injection is a potent analgesic modality for patients presenting for gender-affirming pelvic surgery.

Relative Effects of Various Factors on Ice Ball Formation and Ablation Zone Size During Ultrasound-Guided Percutaneous Cryoneurolysis: A Laboratory Investigation to Inform Clinical Practice and Future Research.

INTRODUCTION: Ultrasound-guided percutaneous cryoneurolysis provides analgesia using cold temperatures to reversibly ablate peripheral nerves. Cryoneurolysis probes pass a gas through a small internal annulus, rapidly lowering the pressure and temperature, forming an ice ball to envelope the target nerve. Analgesia is compromised if a nerve is inadequately frozen, and laboratory studies suggest that pain may be paradoxically induced with a magnitude and duration in proportion with the incomplete ablation. We therefore investigated the relative effects of various factors that may contribute to the size of the ice ball and the effective cryoneurolysis zone. METHODS: A cryoprobe was inserted into a piece of meat, a gas was passed through for 2 min, and the resulting ice ball width (cross-section) and length (axis parallel to the probe) were measured using ultrasound, with the temperature evaluated in nine concentric locations concurrently. RESULTS: The factor with the greatest influence on ice ball size was probe gauge: in all probe types, a change from 18 to 14 increased ice ball width, length, and volume by up to 70%, 113%, and 512% respectively, with minimum internal temperature decreasing as much as from -5 to -32 °C. In contrast, alternating the type of meat (chicken, beef, pork) and the shape of the probe tip (straight, coudé) affected ice ball dimensions to a negligible degree. The ice ball dimensions and the zone of adequate temperature drop were not always correlated, and, even within a visualized ice ball, the temperature was often inadequate to induce Wallerian degeneration. CONCLUSIONS: Percutaneous probe design can significantly influence the effective cryoneurolysis zone; visualizing a nerve fully encompassed in an ice ball does not guarantee adequate treatment to induce the desired Wallerian degeneration because ice forms at temperatures between 0 and -20 °C, whereas only temperatures below -20 °C induce Wallerian degeneration. The correlation between temperatures in isolated pieces of meat and perfused human tissue remains unknown, and further research to evaluate these findings in situ appears highly warranted.

Carbohydrate Loading and Aspiration Risk in Bariatric Patients: Safety in Preoperative Enhanced Recovery Protocols.

BACKGROUND: Enhanced recovery protocols have been developed to improve perioperative outcomes; however, there is ongoing concern for aspiration with recent oral intake in patients with obesity, who may be predisposed to impaired gastrointestinal motility and greater gastric volumes. We aim to study the safety of a 300-mL preoperative carbohydrate-loading drink preceding bariatric surgery. STUDY DESIGN: Data were collected prospectively from patients undergoing primary bariatric surgery. All bariatric patients at our institution are prescribed a proton pump inhibitor for 4 weeks before surgery and undergo a screening preoperative esophagogastroduodenoscopy (EGD) before surgery with a traditional 8-hour fast (NOCARB), followed by an intraoperative day-of-operation EGD with carbohydrate loading (CARB) 2 to 4 hours before incision. Gastric volumes and pH are measured after being endoscopically suctioned via direct visualization during both settings. RESULTS: We identified 203 patients: 94 patients (46.3%) in the CARB group and 109 patients (53.7%) in the NOCARB group. The patients were 82.3% female with a mean age of 42.8 years and average BMI of 41.7 kg/m 2 . There was no difference in gastric volume between NOCARB and CARB (17.0 vs 16.1 mL, p = 0.59). The NOCARB group had lower pH values than the CARB group (2.8 vs 3.8, p = 0.001). Subset analysis of 23 patients who had measurements on both screening and intraoperative EGD revealed lower gastric volumes in CARB patients (13.3 vs 18.3, p < 0.0001). CONCLUSIONS: When included in an enhanced recovery protocol, proton pump inhibitor use and preoperative carbohydrate loading 2 to 4 hours before bariatric surgery does not increase aspiration risk based on gastric volumes and pH and should be strongly considered in all eligible bariatric patients.

A Neural Network Model Using Pain Score Patterns to Predict the Need for Outpatient Opioid Refills Following Ambulatory Surgery: Algorithm Development and Validation.

BACKGROUND: Expansion of clinical guidance tools is crucial to identify patients at risk of requiring an opioid refill after outpatient surgery. OBJECTIVE: The objective of this study was to develop machine learning algorithms incorporating pain and opioid features to predict the need for outpatient opioid refills following ambulatory surgery. METHODS: Neural networks, regression, random forest, and a support vector machine were used to evaluate the data set. For each model, oversampling and undersampling techniques were implemented to balance the data set. Hyperparameter tuning based on k-fold cross-validation was performed, and feature importance was ranked based on a Shapley Additive Explanations (SHAP) explainer model. To assess performance, we calculated the average area under the receiver operating characteristics curve (AUC), F1-score, sensitivity, and specificity for each model. RESULTS: There were 1333 patients, of whom 144 (10.8%) refilled their opioid prescription within 2 weeks after outpatient surgery. The average AUC calculated from k-fold cross-validation was 0.71 for the neural network model. When the model was validated on the test set, the AUC was 0.75. The features with the highest impact on model output were performance of a regional nerve block, postanesthesia care unit maximum pain score, postanesthesia care unit median pain score, active smoking history, and total perioperative opioid consumption. CONCLUSIONS: Applying machine learning algorithms allows providers to better predict outcomes that require specialized health care resources such as transitional pain clinics. This model can aid as a clinical decision support for early identification of at-risk patients who may benefit from transitional pain clinic care perioperatively in ambulatory surgery.

Wearable, noninvasive, pulsed shortwave (radiofrequency) therapy for analgesia and opioid sparing following outpatient surgery: A proof-of-concept case series.

BACKGROUND: It is often difficult to concurrently provide adequate analgesia while minimizing opioid requirements following ambulatory surgery. Nonthermal, pulsed shortwave (radiofrequency) fields are a noninvasive treatment used as an adjunct analgesic and wound healing therapy. The devices may be placed by nursing staff in less than a minute, are relatively inexpensive and readily available, theoretically provide analgesia for nearly any anatomic location, and have no systemic side effects-patients cannot detect any sensations from the devices-or significant risks. Here we present a case series to demonstrate the use of pulsed, electromagnetic field devices for outpatient herniorrhaphy and breast surgery. CASE REPORT: Following moderately painful ambulatory umbilical (n = 3) and inguinal (n = 2) hernia repair as well as bilateral breast surgery (n = 2), patients had taped over their surgical incision(s) 1 or 2 noninvasive, wearable, disposable, pulsed shortwave therapy devices (RecoveryRx, BioElectronics Corporation, Frederick, Maryland) which functioned continuously for 30 days. Average resting pain scores measured on the 0-10 numeric rating scale were a median of 0 during the entire treatment period. Six patients avoided opioid use entirely, while the remaining individual required only 5 mg of oxycodone during the first postoperative day. CONCLUSIONS: These cases demonstrate that the ambulatory use of pulsed shortwave devices is feasible and may be an effective analgesic, possibly obviating opioid requirements following outpatient herniorrhaphy and breast surgery. Considering the lack of any side effects, adverse events, and misuse/dependence/diversion potential, further study with a randomized, controlled trial appears warranted.

Percutaneous Auricular Nerve Stimulation (Neuromodulation) for Analgesia and Opioid-Sparing Following Knee and Hip Arthroplasty: A Proof-of-Concept Case Series.

We present a case series to demonstrate proof-of-concept for the off-label use of an auricular neuromodulation device-originally developed to treat symptoms associated with opioid withdrawal-to instead provide analgesia and opioid-sparing following knee and hip arthroplasties. Within the recovery room, an auricular neuromodulation device (near-field stimulator system 2 [NSS-2] Bridge, Masimo) was applied to 5 patients. Average daily pain at rest and while moving was a median of 0 to 2 as measured on the 0 to 10 numeric rating scale, while median daily oxycodone use was 0 to 2.5 mg until device removal at home on postoperative day 5. One patient avoided opioid use entirely.

The association of Serratus Anterior Plane blocks with postoperative opioid use and analgesia following simple lumpectomy: a retrospective cohort analysis.

BACKGROUND: The potential benefit of regional interventions for simple lumpectomy breast cancer surgeries has not been well investigated. Understanding which patients to not offer a regional intervention to can be just as important as knowing which would benefit. It is unclear whether fascial plane blocks, such as serratus anterior plane (SAP) block, should be routinely performed for less extensive breast surgeries. Therefore, our goal in this retrospective cohort study was to evaluate the association of integrating SAP blocks into a standard perioperative multimodal analgesia plan in patients undergoing simple lumpectomies (without node biopsies) with perioperative opioid consumption. As secondary outcomes, we also analyzed postoperative pain scores and post-anesthesia care unit (PACU) length of stay. METHODS: This was a single institution retrospective cohort study (surgical site infiltration only versus SAP block cohorts) assessing the association of SAP blocks to our outcomes of interest. In the adjusted analysis, we created matched cohorts using 1:1 (surgical site infiltration only: SAP block) propensity-score matching using nearest neighbor-matching without replacement. To compare the primary and secondary outcomes in the matched cohorts, we used the Wilcoxon signed rank test. A P-value of < 0.05 was considered statistically significant. RESULTS: There were 419 patients included in the analysis, in which 116 (27.7%) received a SAP block preoperatively in addition to our standard perioperative analgesia plan. In an unadjusted analysis, no differences were seen in perioperative opioid consumption, PACU pain scores, and PACU length of stay. Among the matched cohorts, the median [quartile] perioperative opioid consumption in the surgical site infiltration only versus SAP block cohorts were 10 mg [10, 13.25 mg] and 10 mg [7, 15 mg], respectively (P = 0.16). No differences were seen in the other outcomes. CONCLUSIONS: In this study, we evaluated the impact of SAP blocks on patients undergoing simple lumpectomies, which are relatively less involved breast surgeries. We concluded that routine use of preoperative regional anesthesia is not beneficial for these specific patients. Future studies should focus on identifying patients that would directly benefit from regional interventions.

Treating Intractable Postamputation Pain with Noninvasive, Wearable, Nonthermal, Pulsed Shortwave (Radiofrequency) Therapy: A 12-Patient Case Series.

BACKGROUND Postamputation phantom and residual limb pain are common and frequently intractable, with few reliably effective treatments. Pulsed nonthermal shortwave (radiofrequency) electromagnetic field therapy is a noninvasive treatment used previously as an adjunct analgesic and wound healing therapy. Its use for postamputation pain remains unexamined. CASE REPORT Twelve patients with an above or below knee amputation with persistent, intractable phantom and/or residual limb pain unresponsive to multiple previous invasive treatments were provided with a noninvasive, wearable, pulsed electromagnetic field device (RecoveryRx, BioElectronics Corporation, Frederick, MD, USA). Patients used the included dressings to self-apply the 12 cm-diameter ringed antenna to their residual limb and then activated the device, which delivered nonthermal radiofrequency energy continuously for up to 30 days. Of the 12 individuals, 4 (33%) experienced minimal/no change, 7 (58%) rated their phantom and/or residual limb pain as "very much improved" at the conclusion of treatment, and 1 (8%) patient reported "moderate" improvement, using the Patient Global Impression of Change scale. Of the 8 responders, worst and average phantom limb pain improved a mean (SD) of 4.0 (2.9) and 4.2 (1.8) points on the 0 to 10 numeric rating scale, respectively. Worst and average residual limb pain improved 5.4 (3.7) and 3.5 (2.4) points, respectively. CONCLUSIONS These cases suggest that pulsed electromagnetic field therapy may be an effective treatment for intractable postamputation pain. Considering the low patient burden of noninvasive, wearable devices, combined with few contraindications and no significant side effects or adverse events, further study with a randomized, controlled trial is warranted.

Preoperative Ultrasound-guided Percutaneous Cryoneurolysis for the Treatment of Pain after Mastectomy: A Randomized, Participant- and Observer-masked, Sham-controlled Study.

BACKGROUND: Ultrasound-guided percutaneous cryoneurolysis is an analgesic technique in which a percutaneous probe is used to reversibly ablate a peripheral nerve(s) using exceptionally low temperature, and has yet to be evaluated with randomized, controlled trials. Pain after mastectomy can be difficult to treat, and the authors hypothesized that the severity of surgically related pain would be lower on postoperative day 2 with the addition of cryoanalgesia compared with patients receiving solely standard-of-care treatment. METHODS: Preoperatively, participants at one enrolling center received a single injection of ropivacaine, 0.5%, paravertebral nerve block at T3 or T4, and perineural catheter. Participants subsequently underwent an active or sham ultrasound-guided percutaneous cryoneurolysis procedure of the ipsilateral T2 to T5 intercostal nerves in a randomized, patient- and observer-masked fashion. Participants all received a continuous paravertebral block with ropivacaine, 0.2%, until the early morning of discharge (usually postoperative day 2). The primary endpoint was the average pain level measured using a 0 to 10 numeric rating scale the afternoon of postoperative day 2. Participants were followed for 1 yr. RESULTS: On postoperative day 2, participants who had received active cryoneurolysis (n = 31) had a median [interquartile range] pain score of 0 [0 to 1.4] versus 3.0 [2.0 to 5.0] in patients given sham (n = 29): difference -2.5 (97.5% CI, -3.5 to -1.5), P < 0.001. There was evidence of superior analgesia through month 12. During the first 3 weeks, cryoneurolysis lowered cumulative opioid use by 98%, with the active group using 1.5 [0 to 14] mg of oxycodone compared with 72 [20 to 120] mg in the sham group (P < 0.001). No oral analgesics were required by any patient between months 1 and 12. After 1 yr chronic pain had developed in 1 (3%) active compared with 5 (17%) sham participants (P < 0.001). CONCLUSIONS: Percutaneous cryoneurolysis markedly improved analgesia without systemic side effects or complications after mastectomy.

Percutaneous auricular nerve stimulation (neuromodulation) for the treatment of pain following outpatient surgery: a proof-of-concept case series.

BACKGROUND: Following outpatient surgery, it is often difficult to provide adequate analgesia while concurrently minimizing opioid requirements. Ultrasound-guided percutaneous peripheral nerve stimulation has been proposed as an analgesic, but requires physician-level skills, advanced equipment, up to an hour to administer, and is frequently cost prohibitive. In contrast, percutaneous auricular neuromodulation may be placed by nursing staff in a few minutes without additional equipment, theoretically provides analgesia for nearly any anatomic location, lacks systemic side effects, and has no significant risks. We now present a case report to demonstrate proof of concept for the off-label use of an auricular neuromodulation device-originally developed to treat symptoms associated with opioid withdrawal-to instead provide analgesia following outpatient surgery. CASE PRESENTATION: Following moderately painful ambulatory orthopedic and breast surgery, seven patients had an auricular neuromodulation device (NSS-2 Bridge, Masimo, Irvine, California, USA) affixed within the recovery room in approximately 5 min and discharged home. Average resting and dynamic pain scores measured on the 0-10 Numeric Rating Scale were a median of 1 over the first 2 days, subsequently falling to 0. Five patients avoided opioid use entirely, while the remaining two each consumed 5 mg of oxycodone during the first 1-2 postoperative days. After 5 days, the devices were removed at home and discarded. CONCLUSIONS: These cases demonstrate that ambulatory percutaneous auricular neuromodulation is feasible and may be an effective analgesic and decreasing or even negating opioid requirements following outpatient surgery. Considering the lack of systemic side effects, serious adverse events, and misuse/dependence/diversion potential, further study with a randomized, controlled trial appears warranted.

Percutaneous auricular nerve stimulation (neuromodulation) for the treatment of pain: A proof-of-concept case report using total joint arthroplasty as a surrogate for battlefield trauma.

BACKGROUND: There are few effective pain treatments following trauma on the battlefield other than opioids, which are limited by respiratory depression. Ultrasound-guided percutaneous peripheral nerve stimulation ("neuromodulation") has been proposed as an analgesic, but requires physician-level skills, advanced equipment, and an hour to administer. In contrast, percutaneous auricular neuromodulation may be placed by a medic in the field under nonsterile conditions in a few minutes, theoretically provides analgesia for any anatomic location, has no side effects, and no significant risks. It therefore offers the potential to be applied quickly on the battlefield without any of the limitations of opioids. We propose total joint replacement as a surrogate for battlefield trauma and here present a case report to demonstrate proof of concept. METHODS: Following open total knee or hip arthroplasty under spinal anesthesia, two patients had an auricular neuromodulation device applied within the recovery room. Patients were discharged with the unit and contacted daily for 7 days. RESULTS: The devices were each applied in under 3 minutes without difficulty, were well tolerated during use, and removed without complication at home on Day 5. During use, neither patient experienced pain while lying, sitting, or ambulating. Neither required analgesics other than scheduled celecoxib; and a single tablet (50 mg) of tramadol for one patient on postoperative Days 3 and 4 for pain while lowering herself to a seated position. On Days 6 and 7, both patients experienced an increase in pain, one of whom required around-the-clock tramadol. CONCLUSION: Ambulatory postoperative percutaneous auricular neuromodulation is feasible. In these two cases, it appears to have markedly reduced pain scores and opioid requirements free of systemic side effects during the week following major orthopedic surgery. Considering the potential of this modality to treat trauma on the battlefield without systemic side effects, additional investigation appears warranted. LEVEL OF EVIDENCE: Therapeutic/care management; Level V.

Predictive Analytics for Inpatient Postoperative Opioid Use in Patients Undergoing Mastectomy.

INTRODUCTION: The use of opioids in mastectomy patients is a particular challenge, having to balance the management of acute pain while minimizing risks of continuous opioid use postoperatively. Despite attempts to decrease postmastectomy opioid use, including regional anesthetics, gabapentinoids, topical anesthetics, and nonopioid anesthesia, prolonged opioid use remains clinically significant among these patients. The goal of this study is to identify risk factors and develop machine-learning-based models to predict patients who are at higher risk for postoperative opioid use after mastectomy. METHODS: In this retrospective cohort study, we collected data from patients that underwent mastectomy procedures. The primary outcome of interest was defined as oxycodone milligram equivalents (OME) greater than or equal to the 75% of OME use on a postoperative day 1. Model performance (area under the receiver-operating characteristics curve (AUC)) of various machine learning approaches was calculated via 10-fold cross-validation. Odds ratio (OR) and 95% confidence intervals (CI) were reported. RESULTS: There were a total of 148 patients that underwent mastectomy and were included. The medium (quartiles) postoperative day 1 opioid use was 5 mg OME (0.25 mg OME). Using multivariable logistic regression, the most protective factors against higher opioid use was being postmenopausal (OR: 0.13, 95% CI: 0.03-0.61, p = 0.009) and cancer diagnosis (OR: 0.19, 95% CI: 0.05-0.73, p = 0.01). The AUC was 0.725 (95% CI: 0.572-0.876). There was no difference in the performance of other machine-learning-based approaches. CONCLUSIONS: The ability to predict patients' postoperative pain could have a significant impact on preoperative counseling and patient satisfaction.