Genome-wide association studies with experimental validation identify a protective role for B lymphocytes against chronic post-surgical pain.

BACKGROUND: Chronic post-surgical pain (CPSP) significantly impacts patients' recovery and quality of life. Although environmental risk factors are well-established, genetic risk remains less understood. METHODS: A meta-analysis of genome-wide association studies followed by partitioned heritability was performed on 1350 individuals across five surgery types: hysterectomy, mastectomy, abdominal, hernia, and knee. In subsequent animal studies, withdrawal thresholds to evoked mechanical stimulation were measured in Rag1 null mutant and wild-type mice after plantar incision and laparotomy. Cell sorting by flow cytometry tracked recruitment of immune cell types. RESULTS: We discovered 77 genome-wide significant single-nucleotide polymorphism (SNP) hits, distributed among 24 loci and 244 genes. Meta-analysis of all cohorts estimated a SNP-based narrow-sense heritability for CPSP at ∼39%, indicating a substantial genetic contribution. Partitioned heritability analysis across a wide variety of tissues revealed enrichment of heritability in immune system-related genes, particularly those associated with B and T cells. Rag1 null mutant mice lacking both T and B cells exhibited exacerbated and prolonged allodynia up to 42 days after surgery, which was rescued by B-cell transfer. Recruitment patterns of B cells but not T cells differed significantly during the first 7 days after injury in the footpad, lymph nodes, and dorsal root ganglia. CONCLUSIONS: These findings suggest a key protective role for the adaptive immune system in the development of chronic post-surgical pain.

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.

Combination of Superficial and Deep Blocks with Rivaroxaban.

OBJECTIVE: Rivaroxaban is a new Xa inhibitor indicated for thromboprophylaxis in patients undergoing joint arthroplasty. This study was designed to assess the risk of major bleeding from the combination of either a single or a continuous deep, superficial, and plexus block and the use of rivaroxaban for thromboprophylaxis following joint arthroplasty. METHOD: Patients undergoing either primary, redo, unilateral, or bilateral total hip or knee replacement while receiving a femoral, sciatic, lumbar plexus nerve block alone or in combination and receiving at least one dose of rivaroxaban 10 mg once a day for thromboprophylaxis postoperatively were included in this analysis. RESULTS: In this series, 766 patients (199 total hip replacements and 567 total knee replacements) were included. A total of 1,104 blocks were performed including 1,029 continuous blocks (509 femoral, 320 sciatic, and 200 lumbar plexus). No major bleeding related to the performance of peripheral nerve blocks was recorded. In contrast, three patients developed hematomas in the operated knee requiring a surgical evacuation. Minor bleeding was recorded at the surgical site in 12 patients vs 10 patients at the site of the block. Although all minor bleeding at the surgical site occurred after the initiation of the rivaroxaban therapy, 80% of minor bleeding at the site of the block was recorded before the initiation of thromboprophylaxis. CONCLUSION: Our data supports the concept that there is no increased risk of major bleeding when deep and superficial blocks are performed in combination in patients receiving thromboprophylaxis rivaroxaban following joint arthroplasty.

The use of intravenous infusion or single dose of low-dose ketamine for postoperative analgesia: a review of the current literature.

OBJECTIVE: As an analgesic and N-methyl-D-aspartate receptor antagonist, ketamine has been increasingly used as an adjunct in the management of acute perioperative pain. Although several meta-analyses have examined low-dose intravenous (i.v.) ketamine, they do not distinguish between different types of infusions. Additionally, the many clinical trials published on ketamine vary by regimen of administration and surgical site. This review seeks to exclusively examine the evidence supporting the use of low-dose i.v. infusion of ketamine for the management of perioperative pain. METHODS: We searched Medline for any clinical trials or meta-analyses that were conducted on low-dose i.v. infusion of ketamine between 1966 and November 2013. Using six equations, we were left with 695 references. Of those, five meta-analyses and 39 clinical trials met the criteria to be included our review. These clinical trials represent 2,482 patients, 1,403 of whom received ketamine. We then examined the efficacy of low-dose i.v. ketamine by regimen and site of surgery using pain scores and opioid consumption as endpoints. Finally, we assessed the safety and long-term impact of low-dose ketamine. RESULTS: Low-dose i.v. ketamine reduces opioid consumption by 40%. It also lowers pain scores, but these findings are less clear. No major complications have been reported with low-dose i.v. infusion of ketamine when given up to 48 hours after surgery. While our review lends support to using low-dose i.v. infusion of ketamine in the management of perioperative pain, its optimal dose and regimen remain to be determined. CONCLUSIONS: Thirty-nine clinical trials assessed a continuous infusion or a bolus of low-dose ketamine for postoperative analgesia using reduction of pain scores or reduction of the opioid consumption as the primary endpoint. The mean reduction of opioid consumption when using low-dose i.v. infusion ketamine (infusion rate less than 1.2 mg/kg/h) is 40%. Ketamine also reduces pain scores, but the amplitude of the effect is less clear. No major complications have been reported with low-dose i.v. infusion of ketamine up to 48 hours following surgery.

Impact of peripheral nerve block with low dose local anesthetics on analgesia and functional outcomes following total knee arthroplasty: a retrospective study.

OBJECTIVE: While the safety and efficacy of peripheral nerve blocks for postoperative pain management has been established in several well controlled prospective trials, the local anesthetic (LA) concentration and volume used in these studies was associated with a significant increase muscle weakness due to motor nerve block. The purpose of the present retrospective study of patients undergoing total knee arthroplasty was to assess the relative analgesic efficacy and functional outcomes of the low concentration, low volume of LA used in peripheral nerve blocks for postoperative pain management. METHODS: Twenty-four months of deidentified patient data were extracted from an electronic medical record system. All patients received opioids with or without continuous femoral and sciatic nerve block infusions for postoperative analgesia. Pain (resting and with activity), cumulative opioid and LA use were primary endpoints, participation in physical therapy (PT), muscle strength deficits and length of hospital stay (LOS) were secondary endpoints. RESULTS: Postoperative pain and opioid use were significantly lower in patients with peripheral nerve blocks (n = 1,329) than those with opioids alone (n = 439). There was no detectable decrease in strength associated with nerve blocks, while a significantly greater proportion of patients with nerve blocks were able to participate in PT on postoperative day 1 (96.4% vs 57.1%). These differences were not due to the impact of the surgeon per se, but whether or not the surgeon used nerve blocks for pain management. There was a small but statistically significant decrease in the average LOS in patients with blocks. CONCLUSION: This analysis supports the use of low concentration, low volume of LA based peripheral nerve blocks for postoperative pain management.

Ropivacaine 0.1% versus 0.2% for continuous lumbar plexus nerve block infusions following total hip arthroplasty: a randomized, double blinded study.

OBJECTIVE: Continuous lumbar plexus blocks provide excellent analgesia for total hip arthroplasty (THA), but their utility has been questioned as they may increase motor weakness. The aim of this study was to compare the efficacy of two different concentrations of ropivacaine on both postoperative analgesia and motor function. METHODS: Thirty patients were examined in this prospective, single center, double-blinded, parallel group, comparative, randomized controlled trial in patients undergoing primary THA. Lumbar plexus catheters were inserted preoperatively. After surgery, patients were randomly assigned to receive an infusion of ropivacaine at a concentration of either 0.1% (group 0.1%) or 0.2% (group 0.2%) at a standardized volume of 7 mL per hour for 24 hours. Patients were also given free access to patient-controlled analgesia hydromorphone for 24 hours, supplemental intravenous (IV) opiates, and boluses of their assigned local anesthetic concentration via the lumbar plexus catheter. The primary endpoint was total hydromorphone consumption in 24 hours. Secondary endpoints included pain scores, sensory and motor function, and patient satisfaction. RESULTS: There was no significant difference in hydromorphone consumption in the first 24 hours postoperatively (mean [95% confidence interval]) between group 0.1% (8.02 mg [6.02-10.02]) and group 0.2% (8.21 mg [5.75-10.69], P = 0.90). The volume of local anesthetic received, pain scores, sensory and motor function, and patient satisfaction did not vary between groups. CONCLUSIONS: Following primary THA, lumbar plexus perineural infusion of 0.1% ropivacaine provided similar benefits for postoperative analgesia and functional recovery as 0.2% ropivacaine.

The design and methods of genetic studies on acute and chronic postoperative pain in patients after total knee replacement.

OBJECTIVE: Total knee replacement (TKR) is the treatment option of choice for the millions of individuals whose osteoarthritis pain can no longer be managed through non-invasive methods. Over 500,000 TKRs are performed annually in the United States. Although most patients report improvement in pain and functioning following TKR, up to 30% report persistent pain that interferes with daily function. However, the reasons for poor outcomes are not clear. To best determine which patients are at risk for pain post TKR, a detailed and comprehensive approach is needed. In this article, we present the methodology of a study designed to identify a set of genetic, proteomic, clinical, demographic, psychosocial, and psychophysical risk factors for severe acute and chronic pain post TKR. DESIGN: Prospective longitudinal observational study. SETTING: University Hospital System. SUBJECTS: Patients scheduled for unilateral TKR with a target number of 150. METHODS: Prior to surgery, we collect demographic, psychosocial, and pain data. Biological data, including blood samples for genetic analyses, and serum, urine, and joint fluid for cytokine assessment are collected intraoperatively. Pain assessments as well as medication use are collected during each of the three days postsurgery. Additionally, pain and psychosocial information is collected 6 and 12 months following surgery. CONCLUSIONS: This study, for the first time, captures the information on both genetic and "environmental" risk factors for acute and chronic pain post-TKR and has the potential to lead to the next step-multicenter large-scale studies on predictors and biomarkers of poor TKR outcomes as well as on tailored interventions and personalized medicine approaches for those at risk.

Sugammadex is effective in reversing rocuronium in the presence of antibiotics.

BACKGROUND: The effectiveness of sugammadex in reversing rocuronium-induced neuromuscular blockade (NMB) in the presence of drugs that may potentiate NMB remains to be fully established. The aim of this post-hoc analysis of data from a Phase III clinical trial (VISTA; NCT00298831) was to investigate the impact of antibiotics on recovery from rocuronium-induced NMB after administration of sugammadex for reversal, and compared the neuromuscular recovery in patients who received antibiotics preoperatively with those who did not. METHODS: A Phase III, multicenter, open-label study designed to reflect potential use of sugammadex in clinical practice was conducted at 19 sites. Data obtained from patients who received antibiotics were compared with the cohort of patients who underwent the same protocol without antibiotics. Each subject received rocuronium 0.6 mg/kg for muscle relaxation, after which tracheal intubation was performed; patients were also permitted to receive maintenance doses of rocuronium 0.15 mg/kg to maintain the desired level of NMB throughout the operation, as required.. At least 15 min after the last rocuronium dose, patients received sugammadex 4.0 mg/kg for reversal. Neuromuscular monitoring was continued until a train-of-four (TOF) ratio of ≥0.9 was achieved or the anesthetic was discontinued. RESULTS: The presence of antibiotics prior to the administration of sugammadex did not affect the recovery time from rocuronium-induced NMB when sugammadex 4.0 mg/kg was administered at least 15 min after the last dose of rocuronium. In the presence of antibiotics, the geometric mean (95% CI) time from administration of sugammadex 4.0 mg/kg to recovery of the TOF ratio to ≥0.9 was 1.6 (1.4-1.9) min (range: 0.7-10.5 min), compared with 2.0 (1.8-2.3) min (range: 0.7-22.3 min) for patients who did not receive antibiotics. CONCLUSIONS: These findings suggest that prophylactic antibiotic use is unlikely to have a major impact on the recovery time from rocuronium-induced NMB with sugammadex reversal. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00298831.

Is L2 paravertebral block comparable to lumbar plexus block for postoperative analgesia after total hip arthroplasty?

BACKGROUND: Continuous lumbar plexus block (LPB) is a well-accepted technique for regional analgesia after THA. However, many patients experience considerable quadriceps motor weakness with this technique, thus impairing their ability to achieve their physical therapy goals. QUESTIONS/PURPOSES: We asked whether L2 paravertebral block (PVB) provides better postoperative analgesia (defined as decreased postoperative opioid consumption and lower pain scores), better preservation of motor function, and decreased length of hospital stay (LOS) compared to LPB in patients undergoing THA. METHODS: Sixty patients undergoing minimally invasive THA under standardized spinal anesthesia were enrolled in this randomized controlled study. After exclusions, 53 patients were randomized into the L2 PVB (n = 27) and LPB (n = 26) groups. Patient-controlled analgesia was available for 24 hours. Motor and pain assessments were performed in the recovery room and at the end of 24 hours. LOS was also noted. RESULTS: Postoperative opioid consumption during the first 24 hours was less in the LPB group (mean ± SD: 24 ± 15 mg morphine) than in the L2 PVB group (32 ± 15 mg morphine; p = 0.005); however, postoperative pain scores were not different between groups. Postoperative motor and rehabilitation outcomes and LOS were also similar. CONCLUSIONS: Our study demonstrates that use of a LPB results in slightly less morphine consumption but comparable pain scores when compared with continuous L2 PVB. No difference was noted in terms of motor preservation or LOS. Although the difference in morphine consumption was only slightly in favor of the LPB group, the advantage of L2 PVBs noted by previous authors as preservation of motor function, was not seen. At our institute where LPBs have been performed for years, there seems to be no real advantage in switching to L2 PVBs. However, L2 PVB could be a reasonable alternative for operators who are wary of LPBs due to their high potential for complications and/or requiring advanced skills for its placement. But, since L2 PVBs are relatively new, not much is known about their complication profile. We recommend a thorough understanding of both techniques before attempting to place them. LEVEL OF EVIDENCE: Level I, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

The effectiveness of ambulatory continuous peripheral nerve blocks for postoperative pain management in children and adolescents.

BACKGROUND: Ambulatory continuous peripheral nerve blocks (CPNBs) are feasible for pediatric patients. We sought to evaluate the efficacy of CPNBs in a pediatric population. METHODS: This retrospective report of 33-month prospectively collected data investigates patient, parent, and nurse pain control satisfaction score (PCSS), the incidence and severity of pain, daily analgesic consumption following discharge home with various CPNBs and On-Q pumps, and any complications and side effects related to CPNBs. RESULTS: Four hundred and three patients (403; aged 5-22) were discharged home with 410 CPNBs (brachial and lumbar plexus, femoral, sciatic, and paravertebral); 76.7% on the day of surgery. The median/interquartile range (IQR) ropivacaine continuous infusion via On-Q pump was 0.24 (0.20-0.30) mg·kg(-1)·hr(-1), and the median/IQR duration was 72 (48-72) h. The median/IQR home PCSS was 10 (9-10). Median Postoperative Ambulatory Care Unit (PACU)/IQR pain control satisfaction scores were 10 (8-10) for the patient, 10 (9-10) for the parent, and 10 (9-10) for the nurse. Thirty-three (10.0%) patients did not report any pain at home, and median maximum home/IQR pain score was 4 (2-6). In the PACU, 126 (31.3%) patients did not report any pain and median/IQR pain score was 1 (0-3). No opioids were administered at home for 12 (4.3%) patients and in the PACU for 150 (37.4%). Sixty-three (14.4%) complications and side effects for 58 patients were reported. We report 93.1% ambulatory efficacy of CPNBs. CONCLUSION: Our patients and their caregivers were very satisfied with ambulatory CPNBs. When combined with oral analgesics, CPNBs provided effective home postoperative analgesia.

Nursing time study for the administration of a PRN oral analgesic on an orthopedic postoperative unit.

As needed (PRN) oral opioid analgesics are an integral part of many orthopedic postoperative multimodal pain management regimens. However, the unpredictable nature of this dosing method can lead to disruptions in the process of administering the medication, as well as be an interruption to regular nursing activities. This IRB approved quantitative time study tested the hypothesis that a significant amount of nursing time is required in the administration of PRN oral opioid analgesics on a postoperative orthopedic nursing unit. The purpose of this study is to evaluate the time necessary to complete the required steps related to the administration of PRN oral analgesics. Nurses from 28 nursing shifts used a personal digital assistant (PDA) to record the time needed to complete these steps. We determined that 10.9 minutes is the mean time required to administer PRN oral analgesics on this unit. Other time studies have evaluated the medication administration process as a whole. No time studies related to PRN oral analgesic administration have been reported. In phase I of our project, the data were summarized and will be used as a baseline comparison for phase II, in which we will evaluate an oral PCA medication administration system.

Fostering Innovation in Medical Education: Addressing the Void of Entrepreneurship Education in Anesthesiology and Pain Medicine Through Incubator Clubs.

Fewer than 30% of all medical schools have programs that encourage medical design innovation or entrepreneurship at the trainee level. This is particularly evident in the fields of anesthesiology and pain medicine, where utilizing medical devices constitutes a significant part of a clinician's daily practice. To fix this gap, our institution has developed an incubator club where trainees can learn about medical devices and entrepreneurship. Our goal is to present how this can be incorporated at other institutions because these clubs are a low resource utilization investment that can teach trainees valuable skills in innovation and entrepreneurship.

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.

A multicenter, randomized, controlled study evaluating preventive etanercept on postoperative pain after inguinal hernia repair.

BACKGROUND: Chronic postsurgical pain (CPSP) affects between 5% and 70% of surgical patients, depending on the surgery. There is no reliable treatment for CPSP, which has led to an increased emphasis on prevention. In this study, we sought to determine whether preventive etanercept can decrease the magnitude of postoperative pain and reduce the incidence of CPSP. METHODS: We performed a multicenter, randomized study in 77 patients comparing subcutaneous etanercept 50 mg administered 90 minutes before inguinal hernia surgery with saline. Patients, surgeons, anesthesiologists, the injecting physician, nursing staff, and evaluators were blinded. The primary outcome measure was a 24-hour numerical rating scale pain score. Secondary outcome measures were postanesthesia care unit pain scores, 24-hour opioid requirements, time to first analgesic, and pain scores recorded at 1 month, 3 months, 6 months, and 12 months. RESULTS: Mean 24-hour pain scores were 3.3 (95% confidence interval [CI], 3.2-4.6) in the etanercept and 3.9 (95% CI, 2.6-4.0) in the control group (P=0.22). The mean number of analgesic pills used in the first 24 hours was 4.0 (SD, 2.8) in the treatment versus 5.8 (SD, 4.2) in the control group (P=0.03). At 1 month, 10 patients (29%) in the treatment group reported pain versus 21 (49%) control patients (P=0.08). The presence of pain at 1 month was significantly associated with pain at 3 months (hazard ratio, 0.74; 99% CI, 0.52-0.97; P=0.03). CONCLUSION: Although preventive etanercept was superior to saline in reducing postoperative pain on some measures, the effect sizes were small, transient, and not statistically significant. Different dosing regimens in a larger population should be explored in future studies.

Safety of a novel parenteral formulation of diclofenac after major orthopedic or abdominal/pelvic surgery in a population including anticoagulated, elderly or renally insufficient patients: an open-label, multiday, repeated dose clinical trial.

OBJECTIVE: Decisions to use or avoid nonsteroidal anti-inflammatory drugs (NSAIDs) for postsurgical pain are often influenced by concerns about bleeding and renal adverse effects. The objective of this study was to evaluate the safety of a novel parenteral NSAID, hydroxypropyl-ß-cyclodextrin (HPßCD) diclofenac, in a large postsurgical patient population, with particular focus on bleeding and renal effects. METHODS: This was a large open-label study in adult patients with acute moderate-to-severe pain following major surgery. Patients received ≥2 days of continuous treatment with HPßCD diclofenac, administered as a small-volume bolus injection every 6 hours. Few exclusion criteria were applied in order to reflect surgical patient populations commonly managed in clinical practice. Adverse events (AEs) were recorded throughout the study. The incidences of bleeding- and renal-related AEs were examined in patient subpopulations with known risk factors for NSAID-induced complications: advanced age, pre-existing renal insufficiency, concomitant anticoagulant use, prolonged exposure, elevated dosage, and major surgeries. RESULTS: Of the total 971 patients studied, 38% were ≥65 years old (12% >75 years), 62% received concomitant anticoagulants, and 6% had pre-existing renal insufficiency. HPßCD diclofenac was well tolerated by the patient population. AE rates are presented by risk factor to enable clinicians to better describe renal- or bleeding-related AEs. CONCLUSIONS: In addition to its previously demonstrated efficacy, this study provides evidence of HPßCD diclofenac's safety in a large postsurgical population including anticoagulated, elderly or renally insufficient patients. Because study exclusion criteria were minimal, these findings may be broadly generalizable to populations commonly treated in clinical practice.

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.