Nanotechnology for Pain Management.

Introduction: In the context of the current opioid crisis, non-pharmacologic approaches to pain management have been considered important alternatives to the use of opioids or analgesics. Advancements in nano and quantum technology have led to the development of several nanotransporters, including nanoparticles, micelles, quantum dots, liposomes, nanofibers, and nano-scaffolds. These modes of nanotransporters have led to the development of new drug formulations. In pain medicine, new liposome formulations led to the development of DepoFoam™ introduced by Pacira Pharmaceutical, Inc. (Parsippany, NJ, USA). This formulation is the base of DepoDur™, which comprises a combination of liposomes and extended-release morphine, and Exparel™, which comprises a combination of liposomes and extended-release bupivacaine. In 2021, Heron Therapeutics (San Diego, CA, USA) created Zynrelef™, a mixture of bupivacaine and meloxicam. Advancements in nanotechnology have led to the development of devices/patches containing millions of nanocapacitors. Data suggest that these nanotechnology-based devices/patches reduce acute and chronic pain. Methods: Google and PubMed searches were conducted to identify studies, case reports, and reviews of medical nanotechnology applications with a special focus on acute and chronic pain. This search was based on the use of keywords like nanotechnology, nano and quantum technology, nanoparticles, micelles, quantum dots, liposomes, nanofibers, nano-scaffolds, acute and chronic pain, and analgesics. This review focuses on the role of nanotechnology in acute and chronic pain. Results: (1) Nanotechnology-based transporters. DepoDur™, administered epidurally in 15, 20, or 25 mg single doses, has been demonstrated to produce significant analgesia lasting up to 48 h. Exparel™ is infiltrated at the surgical site at the recommended dose of 106 mg for bunionectomy, 266 mg for hemorrhoidectomy, 133 mg for shoulder surgery, and 266 mg for total knee arthroplasty (TKA). Exparel™ is also approved for peripheral nerve blocks, including interscalene, sciatic at the popliteal fossa, and adductor canal blocks. The injection of Exparel™ is usually preceded by an injection of plain bupivacaine to initiate analgesia before bupivacaine is released in enough quantity from the depofoarm to be pharmacodynamically effective. Finally, Zynrelef™ is applied at the surgical site during closure. It was initially approved for open inguinal hernia, abdominal surgery requiring a small-to-medium incision, foot surgery, and TKA. (2) Nanotechnology-based devices/patches. Two studies support the use of nanocapacitor-based devices/patches for the management of acute and chronic pain. A randomized study conducted on patients undergoing unilateral primary total knee (TKA) and total hip arthroplasty (THA) provided insight into the potential value of nanocapacitor-based technology for the control of postoperative acute pain. The results were based on 2 studies, one observational and one randomized. The observational study was conducted in 128 patients experiencing chronic pain for at least one year. This study suggested that compared to baseline, the application of a nanocapacitor-based Kailo™ pain relief patch on the pain site for 30 days led to a time-dependent decrease in pain and analgesic use and an increase in well-being. The randomized study compared the effects of standard of care treatment to those of the same standard of care approach plus the use of two nanocapacitor-based device/patches (NeuroCuple™ device) placed in the recovery room and kept in place for three days. The study demonstrated that the use of the two NeuroCuple™ devices was associated with a 41% reduction in pain at rest and a 52% decrease in the number of opioid refills requested by patients over the first 30 days after discharge from the hospital. Discussion: For the management of pain, the use of nano-based technology has led to the development of nano transporters, especially focus on the use of liposome and nanocapacitors. The use of liposome led to the development of DepoDur™, bupivacaine Exparel™ and a mixture of bupivacaine and meloxicam (Zynrelef™) and more recently lidocaine liposome formulation. In these cases, the technology is used to prolong the duration of action of drugs included in the preparation. Another indication of nanotechnology is the development of nanocapacitor device or patches. Although, data obtained with the use of nanocapacitors are still limited, evidence suggests that the use of nanocapacitors devices/patches may be interesting for the treatment of both acute and chronic pain, since the studies conducted with the NeuroCuple™ device and the based Kailo™ pain relief patch were not placebo-controlled, it is clear that additional placebo studies are required to confirm these preliminary results. Therefore, the development of a placebo devices/patches is necessary. Conclusions: Increasing evidence supports the concept that nanotechnology may represent a valuable tool as a drug transporter including liposomes and as a nanocapacitor-based device/patch to reduce or even eliminate the use of opioids in surgical patients. However, more studies are required to confirm this concept, especially with the use of nanotechnology incorporated in devices/patches.

Role of the NeuroCuple™ Device for the Postoperative Pain Management of Patients Undergoing Unilateral Primary Total Knee and Hip Arthroplasty: A Pilot Prospective, Randomized, Open-Label Study.

BACKGROUND: The potential effectiveness of the non-pharmacological and nanotechnology-based NeuroCuple™ device in reducing postoperative surgical pain and opioid consumption remains unknown. METHODS: This randomized controlled open-label study was conducted in patients undergoing a primary unilateral total knee or total hip arthroplasty. In the recovery room, patients were randomized to receive either standard of care (control group) or standard of care plus two NeuroCuple™ devices. The outcome variables included pain and opioid consumption (oral morphine equivalent, OME in milligrams). RESULTS: A total of 69 patients were randomized to either the NeuroCuple™ group (n = 38) or the control group (n = 31). Use of the NeuroCuple™ devices was associated with a significant 34% reduction in pain at rest (means of area under the curve: 6.3 vs. 9.5; p = 0.018) during postoperative days 1-3. Opioid consumption was reduced by 9%. More importantly, use of the NeuroCuple™ devices reduced the number of patients requesting an opioid prescription following discharge from the hospital by 52% (26% vs. 55%, p = 0.016). CONCLUSIONS: Our data suggest that the NeuroCuple™ device may be an effective non-pharmacological alternative to opioids to manage postoperative pain following unilateral arthroplasty due to its ability to reduce postoperative opioid use.

Standardizing nomenclature in regional anesthesia: an ASRA-ESRA Delphi consensus study of upper and lower limb nerve blocks.

BACKGROUND: Inconsistent nomenclature and anatomical descriptions of regional anesthetic techniques hinder scientific communication and engender confusion; this in turn has implications for research, education and clinical implementation of regional anesthesia. Having produced standardized nomenclature for abdominal wall, paraspinal and chest wall regional anesthetic techniques, we aimed to similarly do so for upper and lower limb peripheral nerve blocks. METHODS: We performed a three-round Delphi international consensus study to generate standardized names and anatomical descriptions of upper and lower limb regional anesthetic techniques. A long list of names and anatomical description of blocks of upper and lower extremities was produced by the members of the steering committee. Subsequently, two rounds of anonymized voting and commenting were followed by a third virtual round table to secure consensus for items that remained outstanding after the first and second rounds. As with previous methodology, strong consensus was defined as ≥75% agreement and weak consensus as 50%-74% agreement. RESULTS: A total of 94, 91 and 65 collaborators participated in the first, second and third rounds, respectively. We achieved strong consensus for 38 names and 33 anatomical descriptions, and weak consensus for five anatomical descriptions. We agreed on a template for naming peripheral nerve blocks based on the name of the nerve and the anatomical location of the blockade and identified several areas for future research. CONCLUSIONS: We achieved consensus on nomenclature and anatomical descriptions of regional anesthetic techniques for upper and lower limb nerve blocks, and recommend using this framework in clinical and academic practice. This should improve research, teaching and learning of regional anesthesia to eventually improve patient care.

SuRxgWell: study protocol for a randomized controlled trial of telemedicine-based digital cognitive behavioral intervention for high anxiety and depression among patients undergoing elective hip and knee arthroplasty surgery.

BACKGROUND: Mood disorders (anxiety, depression), sleep disorders, and catastrophizing lead to increased post-operative pain perception, increase in postoperative opioid consumption, decreased engagement with physical activity, and increased resource utilization in surgical patients. Psychosocial disorders significantly affect postoperative outcome. Unfortunately, studies focused on perioperative psychological assessment and treatment are scarce. We propose to test whether digital cognitive behavioral intervention (dCBI) can help surgical patients. dCBI such as RxWell™ is a proven treatment for mood disorders in medical patients such as reducing depression in patients with inflammatory bowel disease. We hypothesize that RxWell™ will also be effective in surgical patients. This study aims to test whether RxWell™ can improve preoperative mood disorders and subsequently reduce postoperative pain and opioid requirement in patients scheduled for primary total hip and knee arthroplasty (THA, TKA). We named the trial as the SuRxgWell trial. METHODS: This is a randomized, controlled trial that will enroll primary and unilateral THA or TKA patients with anxiety and/or depression symptoms before surgery to receive the SuRxgWell dCBI program and investigate its impact on postoperative outcomes including postoperative pain, anxiety, depression, sleep disorder, and catastrophizing. After signing an informed consent, subjects will be screened using the PROMIS questionnaires, and subjects with a T-score of ≥ 60 on the short Patient-Reported Outcomes Measurement Information System (PROMIS) 4a Anxiety and/or short PROMIS 4a Depression questionnaires will be randomized to either usual care (control group) or the cognitive behavioral intervention, RxWell™, plus usual care (intervention group). The control group will receive information on how to locate tools to address anxiety and depression, whereas the intervention group will have access to SuRxgWell 1 month prior to surgery and up to 3 months after surgery. The allocation will be 3:1 (intervention to control). Investigators will be blinded, but research coordinators approaching patients and research subjects will not. The primary outcome will be day of surgery anxiety or depression symptoms measured with the PROMIS Short Form v1.0 -Anxiety 4a/Depression and Generalized Anxiety Disorder Measure (GAD-7) and Patient Health Questionnaire (PHQ-8). Secondary end points include measuring other health-related quality of life outcomes including sleep disturbance, fatigue, ability to participate in social roles, pain interference, cognitive function, pain catastrophizing, and physical function. Other secondary outcomes include collecting data about preoperative and postoperative pain scores, and pain medication usage, and orthopedic functional recovery at baseline, day of surgery, and 1, 2, and 3 months after the surgery with the Pain Catastrophizing Scale, the Knee injury and Osteoarthritis Outcome Score (KOOS), and Hip injury and Osteoarthritis Outcome Score (HOOS). In addition, subjects will be asked to complete a GAD-7 and PHQ-8 questionnaires bi-weekly (via the RxWell™ app for the interventional group or REDCAP for the control group). Data about postsurgical complications, and resource utilization will also be recorded. We will also receive monthly reports measuring the usage and engagement of RxWell use for each participant randomized to that arm. The primary hypotheses will be assessed with intention-to-treat estimates, and differences in primary outcome will be tested using independent two sample t-tests. This trial is registered to the ClinicalTrials.gov database (NCT05658796) and supported by the DAPM, UPMC Health Plan, and the NIH. DISCUSSION: Our trial will evaluate the feasibility of digital cognitive behavioral intervention as a perioperative tool to improve anxiety and depression before and after major orthopedic surgery in comparison to education. If digital cognitive behavioral intervention proves to be effective, this might have important clinical implications, reducing the incidence of chronic postsurgical pain and improving outcomes.

Telemedicine-Based Digital Cognitive Behavioral Intervention for Perioperative Anxiety and Depression for Total Knee Arthroplasty.

Introduction: Preoperative anxiety and depression have been shown to increase postoperative pain and opioid consumption by up to 50% in patients undergoing primary unilateral Total Knee Arthroplasty (TKA). We hypothesized that the use of a telemedicine-based digital Cognitive Behavioral Intervention program (RxWell®) started one month prior to surgery would control anxiety and depression prior to surgery. Materials and methods: This was a randomized, controlled trial that enrolled patients undergoing primary unilateral TKA. At least a month prior to surgery, patients who gave consent to participate were asked to complete PROMIS® (Patient-Reported Outcomes Measurement Information System) emotional anxiety short form 8a and PROMIS® emotional depression short form-8a questionnaires. Patients with T-scores of ≥ 57 were randomized to either a no intervention (control group) or a RxWell® program (treatment group) for a month prior to surgery. The primary outcome of this proof-of-concept study was the ability of the RxWell® to normalize patients' PROMIS anxiety T scores. Results: T scores for anxiety and depression among patients randomized to the RxWell® group significantly decreased from 64.3 ± 3.0 at the time of randomization to 58.5 ± 2.6 prior to surgery (n=5, p=0.006), whereas no changes in T scores were recorded in the control group (59.4 ± 4.2 at the time of randomization vs. 57.7 ± 6.2; n=6, p=0.559). Conclusion: These preliminary data suggest that the use of a RxWell® program represents an effective approach to control anxiety and depression prior to surgery. In contrast, it seems that in the absence of treatment, anxiety level remains similar over a month prior to surgery.

Use of Nanotechnology as an Alternative to Opioids for Post-operative Pain Management Following TKA.

Introduction: In response to the current opioid crisis, there is a great interest to develop non-pharmacologic approaches to post-operative pain management for patients undergoing total knee arthroplasty (TKA). Case Report: We report a case of a patient whose post-operative pain following TKA was managed using the newly designed NeuroCuple™ device, a patch based on the use of nanotechnology. The NeuroCuple™ device was placed above the knee by the patient at home. The use of the NeuroCuple™ device allowed the patient completely avoid the use of any opioids at home. Conclusion: Our report suggests that the use of the NeuroCuple™ device may represent an interesting alternative to opioids for the peri-operative management of pain following a primary, unilateral TKA.

Genome-wide association study suggests a critical contribution of the adaptive immune system to chronic post-surgical pain.

Chronic post-surgical pain affects a large proportion of people undergoing surgery, delaying recovery time and worsening quality of life. Although many environmental variables have been established as risk factors, less is known about genetic risk. To uncover genetic risk factors we performed genome-wide association studies in post-surgical cohorts of five surgery types- hysterectomy, mastectomy, abdominal, hernia, and knee- totaling 1350 individuals. Genetic associations between post-surgical chronic pain levels on a numeric rating scale (NRS) and additive genetic effects at common SNPs were evaluated. We observed genome-wide significant hits in almost all cohorts that displayed significance at the SNP, gene, and pathway levels. The cohorts were then combined via a GWAS meta-analysis framework for further analyses. Using partitioned heritability, we found that loci at genes specifically expressed in the immune system carried enriched heritability, especially genes related to B and T cells. The relevance of B cells in particular was then demonstrated in mouse postoperative pain assays. Taken altogether, our results suggest a role for the adaptive immune system in chronic post-surgical pain.

Safety and Efficacy of Zynrelef® in Combination with a Single Unilateral or Bilateral Nerve Block Performed Prior to Surgery.

Purpose: The FDA recently approved Zynrelef® (A viscous solution of extended release of bupivacaine and meloxicam) to be applied at closure and providing postoperative analgesia for 72 hrs. Although the FDA didn't restrict the use of nerve blocks in combination with this formulation, the safety and efficacy of such a combination has yet to be documented. This quality improvement study investigated this combination within the FDA-approved indications. Methods: Selected surgeons at two hospitals were chosen to use Zynrelef®. According to the standard of care, surgeons were also allowed to request single nerve blocks before surgery. The type of nerve blocks (unilateral or bilateral) performed included quadratus lumborum and paravertebral blocks for abdominal surgery, and adductor canal block for total knee replacement. Each block was performed with 20 mL of 0.375% bupivacaine (n=129) or 0.5% of ropivacaine (n=30). Pain scores, opioid consumption, and prescription refill requests at discharge were recorded. Patients discharged on the same day of surgery were separated into two groups-those who received single nerve blocks plus an Zynrelef® (group 1) vs. those receiving Zynrelef® only (group 2) and was analyzed using an un-paired t-test. Results: A total of 184 patients received Zynrelef®, including 25 patients who didn't receive blocks, 44 who received unilateral blocks and 114 who received bilateral blocks. No symptoms suggestive of Local Anesthetic Toxicity (LAST) were observed. The use of the combination was associated with a 50% reduction in the number of patients filling their opioid prescription. Conclusion: This study provides evidence that the combination of a single unilateral or bilateral nerve block with Zynrelef® is safe.

The Role of Inhalation Aromatherapy, Lavender and Peppermint in the Management of Perioperative Pain and Opioid Consumption Following Primary Unilateral Total Hip Arthroplasty: A Prospective, Randomized and Placebo-Controlled Study.

Introduction: Aromatherapy is claimed to be effective for the treatment of psychosocial disorders, but objective evidence of its effectiveness is still lacking. Psychosocial disorders have been demonstrated to increase postoperative pain and opioid consumption by up to 50%. This study was designed to assess the effectiveness of Aromatherapy in controlling postoperative pain and opioid in anxious patients. Methods: This prospective, randomized, placebo-controlled study was conducted on anxious patients who underwent primary unilateral total hip arthroplasty. After obtaining signed informed consent, each patient was asked to complete a PROMIS (Patient-Reported Outcomes Measurement Information System) anxiety survey. Patients whose T score were >57.2 were randomized to either an active treatment (Lavender Peppermint Elequil® aromatab®) or a placebo Elequil®-aromatab® treatment. Demographics, pain, opioid consumption, PONV, and psychosocial surveys were collected on Postoperative Day POD1, POD2, POD7 and POD30. At the time of discharge and on POD30, each patient was asked to complete a satisfaction questionnaire, and they were asked to complete an SF12 survey on POD30. Difference between means was assessed using absolute standardized mean differences. Results: Sixty patients were included in the intend-to-treat analysis. Use of lavender and peppermint was associated with a decrease of 26% in pain (POD7; 0.46), 33% in opioid consumption (POD2; 0.42), and 48% in acetaminophen consumption (POD7; 0.54) and a 78% decrease in PONV (POD2; 0.44). Psychosocial scores decreased following surgery (p=0.001). Overall satisfaction ratings at discharge were similar, as were functional recovery scores. Discussion: Our data provides evidence that in patients with preoperative anxiety, lavender and peppermint aromas decreases postoperative pain and opioid requirement compared to placebo. Additional research is required to conform our data. Conclusion: This randomized placebo control study provides evidence of the usefulness of inhalation of lavender and peppermint aromas in patients undergoing primary unilateral total hip arthroplasty.

NSS-Bridge Device for Post-Cesarean Delivery Analgesia: A Randomized Controlled Trial.

Introduction: Percutaneous auricular nerve stimulation has been used for the treatment of symptoms associated with opioid withdrawal, including abdominal pain, nausea, and general discomfort. However, its potential utility for pain management and opioid minimization after surgery has not been investigated. The purpose of this study was to test the feasibility and acceptability of a trial protocol designed to assess the effectiveness of the NSS2-Bridge device as a non-pharmacologic alternative to opioids after cesarean delivery. Methods: In a randomized control design, healthy women receiving cesarean delivery were randomized to receive the active device, placebo device, or no device. Devices were placed on the ear following cesarean delivery and left in place for 5 days. Feasibility and acceptability of the device was assessed by patient reports of device tolerability (rated on a 100mm visual analog scale where 0 is not tolerable at all and 100 is the most tolerable) as well as qualitative reporting. Additional outcomes assessed included proportion of patients not using opioids in hospital, as well as pain at rest, pain with movement, and total opioid consumption in the hospital and for the first 5 days after surgery. Results: There were 60 patients included in the final analysis. Device tolerability was rated highly, with an average daily score of >75 mm on the visual analog scale. The trial retention rate was 89.7% with most exclusions (42.9%) occurring due to unanticipated development of care complexity (e.g., hemorrhage and additional surgical procedures), with only 1 exclusion (14.3%) due to device discomfort. The active device group achieved the highest proportion of opioid-free hospitalizations (40%) compared to placebo (20%) and no device groups (30%). Pain at rest and with movement was similar between treatment groups. Conclusions: This trial protocol designed to test the efficacy of NSS2-Bridge device for post-cesarean pain management is feasible and acceptable. Larger proportions of patients not using opioids in the active device group justifies additional investigation on device effectiveness in pregnant and postpartum people at highest risk for pain.

Auricular field nerve stimulation using the NSS-2 BRIDGE® device as an alternative to opioids following kidney donor surgery.

OBJECTIVES: The purpose of this study was to investigate the role that the NSS-2 BRIDGE® device, an auricular field nerve stimulator, may play in reducing opioid requirement and pain in kidney donor surgery. It was not a randomized study. Electrophysiologic studies have demonstrated that the stimulation of the cranial nerves produced by the NSS-2 BRIDGE® device modulates the ascending/descending spinal pain pathways, especially at the level of the limbic system. METHODS: The design compared the effects of the NSS-2 BRIDGE® device (NSS 2-BRIDGE® device group; n=10) to a control group (n=10). In both groups, the surgery was performed using the same standard enhanced recovery after surgery protocol based on the use of a multimodal analgesic approach. For the active treatment group, the NSS-2 BRIDGE® device was placed in the post anesthesia care unit. The primary endpoint was opioid requirement (oral morphine equivalent, OME in mg) at 24 h post-surgery. Secondary endpoints included pain (0-10), at 24 and 48 h, time to discharge from the recovery room, incidence of post-operative nausea and vomiting at 24 h, time to oral intake, time to ambulation, and time to discharge from the hospital. Data was analyzed using unpaired t-test and presented as mean ± standard deviation. RESULTS: Compared to control, the use of the NSS-2 BRIDGE® was associated with a 75.4% reduction in OME (33.6 vs. 8.3 mg; p=0.03) and 41.5% reduction in pain (5 vs. 3.28; p=0.06) at 24 h and a 73.3% difference in pain at 48 h (1.6 ± 1.6 vs. 6.0 ± 2.8; p=0.0004). There was no difference in non-opioid analgesics administration between groups. CONCLUSIONS: The tolerability of NSS-2 BRIDGE® device was reported by most to be excellent. This study suggests that the NSS-2 BRIDGE® device may represent a complementary approach for controlling postoperative opioid consumption and pain in patients undergoing kidney donation.

Auricular nerve stimulation using the NSS-2 BRIDGE device to reduce opioid requirement following laparoscopic Roux-en-Y gastric bypass.

BACKGROUND: Evidence supports the use of complementary techniques to reduce pain and opioid use after surgery. The NSS-2 BRIDGE device (NBD; Innovative Health Solutions, Inc., Versailles, Indiana) modulates pain via stimulation of the nucleus of the auricular branch of the cranial nerves at the level of the brainstem and the limbic system. OBJECTIVE: To investigate the role of auricular nerve field stimulation for pain control following gastric bypass surgery. SETTINGS: U.S. academic medical center. METHODS: A total of 18 subjects were included. Subjects were divided in 2 groups: NBD group (n = 8) and a control group (n = 10). The NBD was placed following laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery in the recovery room. The effectiveness of NBD was assessed comparing the relative use of opioid consumption (oral morphine equivalents) and pain (0 = no pain to 10= worst possible pain) at 24 and 48 hours after surgery. In addition, the device tolerability (1-10) was assessed, with 8-10 considered excellent. Data were analyzed using unpaired t tests and presented as mean ± standard deviation. Alpha was set up at .1. RESULTS: Compared with the control group, the use of NBD was associated with a 60.2% reduction in oral morphine equivalents (38.15 vs 15.2 mg; P < .1) and a 28% reduction in pain (5.0 vs 3.6; P = .1) at 24 hours after surgery. The tolerability of NBD was reported to be excellent. CONCLUSIONS: This report suggests that NBD may represent an interesting alternative to control perioperative pain and limit opioid use following bariatric surgery. This needs to be confirmed by a placebo-controlled, randomized study.

Large reduction in opioid prescribing by a multipronged behavioral intervention after major urologic surgery.

BACKGROUND: Surgeons play a pivotal role in combating the opioid crisis that currently grips the United States. Changing surgeon behavior is difficult, and the degree to which behavioral science can steer surgeons toward decreased opioid prescribing is unclear. METHODS: This was a single-institution, single-arm, pre- and postintervention study examining the prescribing of opioids by urologists for adult patients undergoing prostatectomy or nephrectomy. The primary outcome was the quantity of opioids prescribed in oral morphine equivalents (OMEs) after hospital discharge. The primary exposure was a multipronged behavioral intervention designed to decrease opioid prescribing. The intervention had 3 components: 1) formal education, 2) individual audit feedback, and 3) peer comparison performance feedback. There were 3 phases to the study: a pre-intervention phase, an intervention phase, and a washout phase. RESULTS: Three hundred eighty-two patients underwent prostatectomy, and 306 patients underwent nephrectomy. The median OMEs decreased from 195 to 19 in the prostatectomy patients and from 200 to 0 in the nephrectomy patients (P < .05 for both). The median OMEs prescribed did not increase during the washout phase. Prostatectomy patients discharged with opioids had higher levels of anxiety than patients discharged without opioids (P < .05). Otherwise, prostatectomy and nephrectomy patients discharged with and without opioids did not differ in their perception of postoperative pain management, activity levels, psychiatric symptoms, or somatic symptoms (P > .05 for all). CONCLUSIONS: Implementing a multipronged behavioral intervention significantly reduced opioid prescribing for patients undergoing prostatectomy or nephrectomy without compromising patient-reported outcomes.

A Prospective Randomized Trial of an Oral Patient-Controlled Analgesia Device Versus Usual Care Following Total Hip Arthroplasty.

BACKGROUND: Multimodal pain management for surgery patients may include the use of a combination of scheduled oral pain medications with as-needed (PRN) oral opioids. Multiple concurrent time demands on nursing staff frequently cause delays in the delivery of oral PRN pain medication compromising pain management. PURPOSE: Postoperative pain control was compared using a wireless oral patient-controlled analgesia device for the delivery of oxycodone with a control group receiving PRN oxycodone from nursing staff. METHODS: Thirty patients were prospectively randomized into each of 2 groups after total hip arthroplasty. Patient demographics, pain scores, drug dose data, and physical therapy data were collected from chart reviews. Additional data were obtained from patient and nursing surveys. RESULTS: Device patients recorded statistically lower pain scores while taking lower doses of oxycodone on postoperative Day 1 as compared with the control group. Patient surveys indicated that those in the device group reported lower pain scores 24 hours prior to discharge, albeit not statistically different from the control group. Men in the device group reported statistically lower pain scores with physical therapy than men in the control group. Findings from the nursing survey indicate that nurses favored the device over nurse-administered PRN. CONCLUSION: Patients using the wireless patient-controlled analgesia (PCA) (oral) device had less pain at rest and with activity (men) while taking lower doses of oxycodone with each dose. Nursing surveys indicated that nursing staff in this orthopedic postoperative unit found the device easy to use, reliable, and efficient. They also recommended its adoption for those capable of using it.

Effect of multimodal analgesia with paravertebral blocks on biochemical recurrence in men undergoing open radical prostatectomy.

BACKGROUND: Recent studies suggest that anesthetic technique during radical prostatectomy for prostate cancer may affect recurrence or progression. This association has previously been investigated in series that employ epidural analgesia. The objective of this study is to determine the association between the use of a multimodal analgesic approach incorporating paravertebral blocks and risk of biochemical recurrence following open radical prostatectomy. PATIENTS AND METHODS: Using a prospective database of 3,029 men undergoing open radical prostatectomy by a single surgeon, we identified 2,909 men who received no neoadjuvant androgen deprivation and had at least 1 year of follow up. We retrospectively compared patients who received general analgesia with opioid analgesia (1999-2003, n = 662) to those who received general analgesia with multimodal analgesia incorporating paravertebral blocks (2003-2014, n = 2,247). The primary outcome was time to biochemical recurrence. Biochemical recurrence-free interval was assessed using the Kaplan-Meier technique and compared using a multivariate Cox-proportional hazards regression model. RESULTS: In total, 395 patients (14%) experienced biochemical recurrence following radical prostatectomy, including 265 (12%) who received multimodal analgesia and 130 (20%) who did not (adjusted P = 0.27). After adjusting for age, race, body mass index, preoperative prostate specific antigen, grade, stage, perineural invasion, margin status, percent of tumor in the gland, and diameter of the dominant nodule, there was no difference in recurrence-free interval between groups (HR = 0.92, 95% CI: 0.73-1.17). CONCLUSION: Use of a multimodal analgesic approach incorporating paravertebral blocks is not associated with a reduced risk of biochemical recurrence following radical prostatectomy.

Safety of Injectable HPßCD-Diclofenac in Older Patients with Acute Moderate-to-Severe Postoperative Pain: A Pooled Analysis of Three Phase III Trials.

BACKGROUND: Hydroxypropyl-ß-cyclodextrin-diclofenac (HPßCD-diclofenac) is an NSAID used to treat acute moderate-to-severe postoperative pain. This post hoc analysis investigated the safety of HPßCD-diclofenac in patients aged ≥ 65 years. METHODS: Data from three phase III trials of HPßCD-diclofenac in adult patients with acute moderate-to-severe postoperative pain were pooled (NCT00448110, NCT00507026, and NCT00726388). Patients who received one or more dose of HPßCD-diclofenac or placebo were included and stratified according to age: < 65, 65-74, or ≥ 75 years. Numerical and categorical variables were compared across the groups using ANOVA and Cochran-Mantel-Haenszel tests, respectively. Cochran-Mantel-Haenszel relative risks compared with placebo were calculated, adjusted by study. RESULTS: Overall, 1289 patients were included: 878, 282, and 129 in the < 65, 65-74, and ≥ 75-years groups, respectively. Overall incidence of treatment-emergent adverse events (TEAEs) was similar in the three groups (p = 0.4360). Incidences of postoperative anemia (p < 0.0001), constipation (p = 0.0017), and hypotension (p = 0.0003) increased significantly across the age groups, whereas headache (p = 0.0008) and flatulence (p = 0.0118) decreased significantly. Relative risks for all System Organ Class categories and preferred terms investigated were similar among the groups and similar to placebo. CONCLUSIONS: Overall incidence of TEAEs in patients aged 65-74 or ≥ 75 years was similar to patients aged < 65 years. The groups displayed similar relative risks for the most frequent TEAEs, which were all similar to placebo. The TEAE profiles of the groups showed differences, all of which may be anticipated due to age-related differences in susceptibility and the types of surgery most commonly performed in each group. CLINICALTRIALS. GOV IDENTIFIERS: NCT00448110, NCT00507026, and NCT00726388.