Excessive opioid prescriptions after total joint arthroplasty (TJA) increase risks for adverse opioid related events, chronic opioid use, and increase the availability of opioids for unlawful diversion. Thus, decreasing postoperative prescriptions may improve quality after TJA. Concerns exist that a decrease in opioids prescribed may increase complications such as readmissions, emergency department (ED) visits or worsened patient reported outcomes (PROs). The purpose of this quality improvement study was to explore whether a reduction in opioids prescribed after TJA resulted in increased complications. Methods: Data originated from a statewide arthroplasty database (MARCQI). The database collects over 96% of all TJA performed in the state of Michigan, USA. Data was prospectively abstracted and included OMEs prescribed at discharge, readmissions, ED visits within 30 days and PROs. Data was collected one year before and after the creation of an opioid prescribing protocol that had decreased prescriptions by approximately 50% in opioid naive and tolerant patients. Trends were monitored using Shewhart control charts. 84,998 TJA over two-years were included. All groups showed a reduction in opioids prescribed. Importantly, no increased complications occurred concomitant to this reduction. No increases in ED visits or readmissions, and no decreases in KOOSJR/HOOSJR/PROMIS10 scores were noted in any of the groups. Using large data sets and registries can drive performance and improve quality. The MARCQI Postoperative opioid prescription recommendations and performance measures decreased total oral morphine equivalents prescribed over a large and diverse population by approximately 50% without decreasing PROs or increasing ED visits or hospital readmissions. A reduction in opioids prescribed after TJA can be accomplished safely and without an increase in complications across a large population

The current study aims to find the role of Enhance Recovery Pathway (ERP) as a multidisciplinary approach aimed to expedite rapid recovery, reduce LOS, and minimize morbidity associated with Non Fusion Anterior Scoliosis Correction (NFASC) surgery. A retrospective analysis of 35 AIS patients who underwent NFASC with Lenke 1 and Lenke 5 curves with a minimum of 1 year of follow-up was done. Patient demographics, surgical details, postoperative analgesia, mobilization, length of stay (LOS), patient satisfaction survey score with respect to information and care, and 90 days complications were collected. The cohort included 34 females and 1 male with a mean age of 15.2 years at the time of surgery. There were 16 Lenke 1 and 19 Lenke 5 in the study. Mean preoperative major thoracic and thoracolumbar/lumbar Cobb's angle were 52˚±7.6˚ and 51˚±4.5˚ respectively. Average blood loss and surgical time were 102 ±6.4 ml and 168 ± 10.2 mins respectively. Average time to commencing solid food was 6.5±1.5 hrs. Average time to mobilization following surgery was 15.5± 4.3 hrs. The average duration to the stopping of the epidural was 42.5±3.5 hrs. The average dose of opioid consumption intraoperatively was 600.5±100.5 mcg of fentanyl i.v. and 12.5±4.5 mg morphine i.v. Postoperatively opioids were administered via an epidural catheter at a dose of 2 mg of morphine every 24 hours up to 2 days and an infusion of 2mcg/hr of fentanyl along with 0.12-0.15% ropivacaine. The average duration to transition to oral analgesia was 55.5±8.5 hrs .20 patients had urinary catheter and the average time to removal of the catheter was 17.5±1.4 hrs. 25 patients had a chest tube and the average time to remove of chest tube was 25.5±3.2 hrs. The average length of hospital stay was 3.1±0.5 days. No patient had postoperative ileus or requirement of blood transfusion or any other complications. No correlation was found between LOS and initial cobb angle. The application of ERP in AIS patients undergoing NFASC results in reduced LOS and indirectly the cost, reduced post-operative opioid use, and overall improve patient satisfaction score

Introduction and Objective. Continuous peripheral nerve blocks (cPNBs) have shown good results in pain management after orthopedic surgeries. However, the variation of performance between different subspecialities is unknown. The aim of this study is to describe our experience with cPNBs after lower limb orthopedic surgeries in different subspecialties. Materials and Methods. This prospective cohort study was performed on collected data from cPNBs after orthopedic surgeries in lower limbs. Catheters were placed by experienced anesthesiologists using sterile technique. After catheterization, the patients were examined daily, by specially educated acute pain service nurses. The characteristics of the patients, duration of catheterization, severity of the post-operative pain, need for additional opioids, and possible complications were registered. Results. We included 246 patients (=547 catheters). 115 (21%) femoral, 162 (30%) saphenous, 66 (12%) sciatic, and 204 (37%) popliteal sciatic nerve catheter were used. The median duration of a catheter was 3 days [IQR = 2 – 5]. The proportion of femoral, sciatic, saphenous, and popliteal nerve catheters with duration of more than two days was 81%, 79%, 73%, and 71% for, respectively. This proportion varied also between different subspecialties. 91% of the catheters remained in place for more than two days in amputations (n=56), 89% in pediatric surgery (n=79), 76% in trauma (n=217), 64% in foot and ankle surgery (n=129), and 59% in limb reconstructive surgery (n=66). The proportion of pain-free patients were 77 – 95% at rest, 63 – 88% at mobilization. 79 – 92% did not need increased opioid doses, and 50 – 67% did not require PRN opioid. 443 catheters (81%) were removed as planned. The cause of unplanned catheter removal was loss of efficacy in 69 (13%), dislodgement in 23 (4.2%), leakage in 8 (1.5%), and erythema in 4 catheters (0.73%). No major complication occurred. Conclusions. 81% of catheters remained in place until planned removal and opioid usage after surgery was lower than expected. Catheters were efficient in both adult and pediatric surgery; however, a variation was seen between orthopaedic subspecialities regarding duration of nerve catheter usage

Introduction and Objective. Knee osteoarthritis (KOA) is a frequent disease for which therapeutic possibilities are limited. In current recommendations, the first-line analgesic is acetaminophen. However, low efficacy of acetaminophen, frequently leads to the use of weak opioids (WO) despite their poor tolerance, especially in elderly patients. The primary objective was to compare the analgesic efficacy and safety of a new wearable transcutaneous electrical nerve stimulation (W-TENS) to weak opioids (WO) in the treatment of moderate to severe, nociceptive, chronic pain in knee osteoarthritis patients. Materials and Methods. ArthroTENS study is a phase 3, non-inferiority, multicentric, prospective, randomized, single-blinded for primary efficacy outcome, controlled, in 2-parallel groups, clinical study comparing W-TENS versus WO over a 3-month controlled period with an additional, optional, non-controlled, 3-month follow-up for patients in W-TENS group. The co-primary outcome was KOA pain intensity (PI) at month 3 and the number of adverse events (AEs) over 3 months. Results. The non-inferiority of W-TENS was demonstrated in both the PP and ITT populations. At M3, PI in PP population was 3.87 (2.12) compared to 4.66 (2.37) (delta: −0.79 (0.44); 95% CI (−1.65; 0.08)) in W-TENS and WO groups, respectively. Since the absolute value of the 95% CI of the between-treatments mean PI difference [−1.71, – 0.12] was above 0 in ITT set, the planned superiority analysis was performed, demonstrating that W-TENS was significantly superior to WO at M3 (P=0.0124). At M1 and M3, the W-TENS group reached the absolute minimal clinically important difference (MCID) for an analgesic (1.8 (2.1) and 2.1 (2.3), respectively), corresponding to a 20 mm reduction in PI (interquartile range: 15–30) on a 0–100 mm visual analogic scale – i.e. 2 points on a numerical rating scale – which equates to “much better”. Conversely, in the WO group, a 0.5 (1.8) and a 1.1 (2.1) reduction in PI were observed at M1 and M3, respectively, while a 1-point reduction in PI is required to be considered as a “slightly better” improvement. In WO group, AEs were the common systemic AEs reported with WO (nausea, constipation, drowsiness, dizziness, pruritus, vomiting, dry mouth). AEs in W-TENS group were local, such as local cutaneous reaction (erythema). Thirty-nine (70.9%) patients wished to extend W-TENS treatment for 3 additional months. Only one patient discontinued this additional period and results were maintained at M6. Conclusions. W-TENS was more effective and better tolerated than WO in the treatment of nociceptive KOA chronic pain and could represent an interesting non-pharmacological alternative to WO

The risk of falls in patients undergoing orthopedic procedures is particularly significant in terms of health and socioeconomic effects. The literature analyzed closely this risk following procedures performed on the lower limb, but the implications following procedures on the upper limb remain to be investigated. Interestingly, it is not clear whether the increased risk of falling in patients undergoing shoulder surgery is due to preexisting risk factors at surgery or postoperative risk factors, such as anesthesiologic effects, opioid medications used for pain control, or brace use. Only one prospective study examined gait and fall risk in patients using a shoulder abduction brace (SAB) after shoulder surgery, revealing that the brace adversely affected gait kinematics with an increase in the risk of falls. The main purpose of the study was to investigate the influence of SAB on gait parameters in patients undergoing shoulder surgery. Patients undergoing elective shoulder surgery (arthroscopic rotator cuff repair, reverse total shoulder arthroplasty, and Latarjet procedure), who used a 15° SAB in the postoperative period, were included. Conversely, patients age > 65 years old, with impaired lower extremity function (e.g., fracture sequelae, dysmorphism, severe osteo-articular pathology), central and peripheral nervous system pathologies, and cardiac/respiratory/vascular insufficiency were excluded. Participants underwent kinematic analysis at four different assessment times: preoperative (T0), 24 hours after surgery (T1), 1 week after surgery (T2), and 1 week after SAB removal (T3). The tests used for kinematic assessment were the Timed Up and Go (TUG) and the 10-meter test (10MWT), both of which examine functional mobility. Agility and balance were assessed by a TUG test (transitions from sitting to standing and vice versa, walking phase, turn-around), while gait (test time, cadence, speed, and pelvic symmetry) was evaluated by the 10MWT. Gait and functional mobility parameters during 10MWT and TUG tests were assessed using the BTS G-Walk sensor (G-Sensor 2). One-way ANOVA for repeated measures was conducted to detect the effects of SAB on gait parameters and functional mobility over time. Statistical analysis was performed with IBM®SPSS statistics software version 23.0 (SPSS Inc., Chicago, IL, USA), with the significant level set at p<0.05. 83% of the participants had surgery on the right upper limb. A main effect of time for the time of execution (duration) (p=0.01, η2=0.148), speed (p<0.01, η2=0.136), cadence (p<0.01, η2=0.129) and propulsion-right (R) (p<0.05, η2=0.105) and left (L) (p<0.01, η2=0.155) in the 10MWT was found. In the 10MWT, the running time at T1 (9.6±1.6s) was found to be significantly longer than at T2 (9.1±1.3s, p<0.05) and at T3 (9.0±1.3s, p=0.02). Cadence at T1 (109.7±10.9steps/min) was significantly lower than at T2 (114.3 ±9.3steps/min, p<0.01) and T3 (114.3±9.3steps/min, p=0.02). Velocity at T1 (1.1±0.31m/s) was significantly lower than at T2 (1.2± 0.21m/s, p<0.05). No difference was found in the pelvis symmetry index. No significant differences were found during the TUG test except for the final rotation phase with T2 value significantly greater than T3 (1.6±0.4s vs 1.4±0.3s, p<0.05). No statistically significant differences were found between T0 and T2 and between T0 and T3 in any of the parameters analyzed. Propulsion-R was significantly higher at T3 than T1 (p<0.01), whereas propulsion-L was significantly lower at T1 than T0 (p<0.05) and significantly higher at T2 and T3 than T1 (p<0.01). Specifically, the final turning phase was significantly higher at T2 than T3 (p<0.01); no significant differences were found for the duration, sit to stand, mid-turning and stand to sit phases. The results demonstrated that the use of the abduction brace affects functional mobility 24 hours after shoulder surgery but no effects were reported at longer term observations

Osteoarthritis (OA) is a major global disease with increasing prevalence. It is one of the most significant causes of disability worldwide and represents a major burden in terms of healthcare delivery and impact on the quality of life of patients. It is a cause of severe chronic pain and has given rise to alarming levels of opioid use and addiction. Despite this prevalence, there are no disease-modifying treatments which delay or reverse the degrative changes within joints which are characteristics of the disease. All treatments are symptom-modifying with the exception of joint arthroplasty, which is currently the most common surgical procedure carried out in US hospitals. Several pharmaceutical and biological interventions have been tested in recent years, including metalloproteinase inhibitors, chondrogenic agents such as Kartogenin, IL-1 antagonists and monoclonal antibodies. So far, none of these has provided an effective disease-modifying treatment. Cellular therapies have a great deal of promise because of their anti-inflammatory and regenerative effects. Mesenchymal stromal cells (MSCs) have been widely studied as a treatment for OA in preclinical and clinical assessments with generally positive results. As the clinical testing of these cells proceeds serious questions emerge relating to the quality and consistency of the therapeutic product and the need for better standardisation with regard to, for example, the tissue source and expansion conditions. Of equal importance is the need for deeper insight into the therapeutic mechanism, specifically the activity and phenotype of cells transplanted to the OA environment, their fate and interaction with local cells

Introduction. Despite recent national advances in the care for the hip fracture patient, significant morbidity and mortality persists. Some of this morbidity is attributable to the analgesia provided in the hospital setting. The National Institute of Clinical Excellence recommends the use of simple oral analgesia including opioids, with fascia-iliac blocks used as an adjunct. Literature review reveals a paucity of evidence on this topic. The aim of this study was to evaluate the efficacy of fascia iliac blocks through analysis of pre and post-operative opioid usage, post-operative delirium, time to bowel opening and naloxone use. Methods. A retrospective study was performed between September-December 2013. Inclusion criteria were determined. 41 patients who received spinal anaesthesia alone and 41 patients who received spinal anaesthesia and a fascia-iliac block were included. Results. Patients who received a fascia-iliac block received significantly less post-operative and total analgesia (p=0.04, p=0.03), had lower rates of delirium (p=0.03) and those patients which were discharged directly home had a shorter inpatient stay (p=0.03). No patients who received a fascia-iliac block needed naloxone to reverse opioid toxicity, whilst two non fascia iliac block patients did. Conclusions. Fascia iliac blocks either given in A&E or at the time of spinal anaesthesia are a useful adjunct to provide analgesia in the hip fracture patient. The John Radcliffe hospital aims to incorporate fascia-iliac blocks into the care pathway for the hip fracture patient

Robust evidence on the effectiveness of peri-operative local anaesthetic infiltration (LAI) is required before it is incorporated into the pain management regimen for patients receiving total hip replacement (THR). We assessed the effectiveness of LAI using a systematic review and a fully powered randomised controlled trial (RCT) with economic evaluation. We searched MEDLINE, Embase and Cochrane databases for RCTs of peri-operative LAI in patients receiving THR. Two reviewers screened abstracts, extracted data, and liaised with authors. Outcomes were pain, opioid use, mobilisation, hospital stay and complications. If feasible, we conducted meta-analysis. In the APEX RCT, we randomised 322 patients awaiting THR to receive additional peri-operative LAI (60mls 0.25% bupivacaine plus adrenaline) or standard anaesthesia alone. Post-operatively, all patients received patient-controlled morphine. The primary outcome was joint pain severity (WOMAC-Pain) at 12 months. Patients and outcome assessors were blinded to allocation. Within APEX, cost-effectiveness was assessed from the health and social-care perspective in relation to quality adjusted life years (QALYs) and WOMAC-Pain at 12-months. Resource use was collected from hospital records and patient questionnaires. In the systematic review, we identified 13 studies (909 patients). Patients undergoing THR receiving LAI experienced greater pain reduction at 24 hours at rest, standardised mean difference (SMD) −0.61 (95%CI −1.05, −0.16; p=0.008) and at 48 hours during activity, SMD −0.43 (95%CI −0.78, −0.09; p=0.014). Patients receiving LAI spent fewer days in hospital, used less opioids and mobilised earlier. Complications were similar between groups. Long-term outcomes were not a focus of these studies. In the APEX RCT, pain levels in hospital were broadly similar between groups, probably due to patient-controlled analgesia. Opioid use was similar between groups. Time to mobilisation and discharge were largely dependent on local protocols and did not differ between groups. Patients receiving LAI were less likely to report severe pain at 12 months than those receiving standard care, odds ratio 10.2 (95%CI 2.1, 49.6; p=0.004). Complications were similar between groups. In the economic evaluation, LAI was associated with lower costs and greater cost-effectiveness than standard care. Using a £20,000 per QALY threshold, the incremental net monetary benefit was £1,125 (95%CI £183, £2,067) and the probability of being cost-effective was greater than 98 %. The evidence suggests that peri-operative LAI is a cost-effective intervention for reducing acute and chronic post-surgical pain after THR

Robust evidence on the effectiveness of peri-operative local anaesthetic infiltration (LAI) is required before it is incorporated into the pain management regimen for patients receiving total knee replacement (TKR). To assess the effectiveness of peri-operative LAI for pain management in patients receiving TKR we conducted a systematic review, fully powered randomised controlled trial (RCT) and economic evaluation. We searched MEDLINE, Embase and Cochrane databases for RCTs of peri-operative LAI in patients receiving TKR. Two reviewers screened abstracts and extracted data. Outcomes were pain, opioid use, mobilisation, hospital stay and complications. Authors were contacted if required. When feasible, we conducted meta-analysis with studies analysed separately if a femoral nerve block (FNB) was provided. In the APEX RCT, we randomised 316 patients awaiting TKR to standard anaesthesia which included FNB, or to the same regimen with additional peri-operative LAI (60mls 0.25% bupivacaine plus adrenaline). Post-operatively, all patients received patient-controlled morphine. The primary outcome was joint pain severity (WOMAC-Pain) at 12 months. Patients and outcome assessors were blinded to allocation. Within APEX, cost-effectiveness was assessed from the health and social-care perspective in relation to quality adjusted life years (QALYs) and WOMAC-Pain at 12-months. Resource use was collected from hospital records and patient questionnaires. In the systematic review, 23 studies including 1,439 patients were identified. Compared with patients receiving no intervention, LAI reduced WOMAC-Pain by standardised mean difference (SMD) −0.40 (95%CI −0.58, −0.22; p<0.001) at 24 hours at rest and by SMD −0.27 (95%CI −0.50, −0.05; p=0.018) at 48 hours during activity. In three studies there was no difference in pain at any time point between randomised groups where all patients received FNB. Patients receiving LAI spent fewer days in hospital, used less opioids and mobilised earlier. Complications were similar between groups. Few studies reported long-term outcomes. In the APEX RCT, pain levels in hospital were broadly similar between groups. Overall opioid use was similar between groups. Time to mobilisation and discharge were largely dependent on local protocols and did not differ between groups. There were no differences in pain outcomes between groups at 12 months. In the economic evaluation, LAI was marginally associated with lower costs. Using the NICE £20,000 per QALY threshold, the incremental net monetary benefit was £264 (95%CI, −£710, £1,238) and the probability of being cost-effective was 62%. Although LAI appeared to have some benefit for reduced pain in hospital after TKR there was no evidence of pain control additional to that provided by femoral nerve block, however it would be cost-effective at the current NICE thresholds

This edition of Cochrane Corner looks at some of the work published by the Cochrane Collaboration, covering pharmacological interventions for the prevention of bleeding in people undergoing definitive fixation or joint replacement for hip, pelvic, and long bone fractures; interventions for reducing red blood cell transfusion in adults undergoing hip fracture surgery: an overview of systematic reviews; and pharmacological treatments for low back pain in adults: an overview of Cochrane Reviews

Summary Statement. There were significant differences in the pain experience, behaviors, and perceptions on analgesics, between the Australia and Singapore cohorts, after hospital discharge following TKR. These findings may be influenced by the ethnicity and cultural differences between these two countries. Introduction. In recent years the hospital length of stay after total knee replacement (TKR) has shortened. Hence, patients have to self-manage their pain earlier after the surgery. The aim of this study was to examine if the pain experience, self-management behaviors and potential barriers to optimal analgesia after hospital discharge for TKR differed in different ethnicity groups. Patients & Methods. We administered a questionnaire to patients undergoing TKR in 10 Australian hospitals, and one large Singaporean hospital, two weeks following hospital discharge.1 We asked participants about their pain severity, use of analgesics, side-effects, perceptions of analgesics use, and satisfaction with pain relief at home. The two groups were compared using Chi-squared test with SPSS 20.0 with statistical significance set at p < 0.05. Results. 171 (98%) participants from the Australian centers and 105 (94%) from the Singaporean hospital completed the questionnaire. Compared with the Singaporean patients, significantly more participants in the Australian cohort reported that their worst pain period occurred during the first two weeks at home (52% vs. 20%, p < 0.0001), and that their average pain at home was ‘severe/extreme’ (23% vs. 6%, p < 0.0001). More participants in the Australian cohort consumed an opioid alone or in combination with non-opioid analgesics (69% vs. 33%, p < 0.0001). Although many in both cohorts experienced analgesic-related side-effects, the proportion was higher in the Australian cohort (84% vs. 41%, p < 0.0001). A very much larger proportion of participants in the Australian cohort sought further medical help for their pain (60% vs. 3%, p < 0.0001). A much small proportion of patients in the Australian cohort perceived that analgesics could not control pain (26% vs. 44%, p = 0.002); were concerned about addiction (26% vs. 42%, p = 0.005) or developing tolerance to analgesics (28% vs. 49%, p < 0.0001); or preferred enduring pain than analgesic-related side-effects (25% vs. 42%, p < 0.002). There was no significant difference in satisfaction with analgesia between the two cohorts (64% vs. 74%, p = 0.179). Discussion/Conclusion. Following hospital discharge for TKR, there were differences in the pain experience, opioid consumption, side-effects, and perceptions of analgesics, between the Australian and Singaporean cohorts. Ethnic or cultural differences might have influenced the differences found, as the Australian cohort mostly comprised of Caucasians while the Singaporean cohort comprised exclusively patients of Asian origin. Interestingly, despite more participants in the Australian cohort experiencing severe pain and higher incidence of analgesic-related side-effects, the proportion who were satisfied with analgesia during the first two weeks after hospital discharge were similar, suggesting that satisfaction is a complex concept influenced by the interplay of many factors. Future studies are required to examine the extent to which ethnicity and cultural factors determine the pain intensity, behaviours and perceptions reported by patients after TKR

Background. Adequate pain management is mandatory for patients' early rehabilitation and improvement of outcome after total knee arthroplasty (TKA). Conventional pain management, consisted of mainly opioids, has some adverse effects such as dizziness and nausea. Motor blockade occasionally resulted from epidural analgesics. A novel multimodal analgesic strategy with peripheral nerve block, peri-articular injection (PAI) and intravenous patient controlled analgesia (IVPCA) were utilized for our patients receiving TKA. In this study, we compared the clinical efficacy and adverse effects in the group of multimodal analgesia (MA) or epidural analgesia alone. Methods. One hundred and eighteen patients undergoing TKA with spinal anesthesia were enrolled. Patients of TKA received either our protocol of multimodal analgesia or patient controlled epidural analgesia (PCEA) alone. MA included ultrasound guided nerve block in femoral and obturator nerves before spinal anesthesia, and PAI mixed with NSAID, morphine, ropivacaine and epinephrine, as well as IVPCA after surgeries. The analgesic effect with numeric rating scale (NRS) and occurrence of adverse effects, including motor blockade, numbness, postoperative nausea/vomiting (PONV), and dizziness were recorded for all patients. Results. Thirty-one patients received MA, and eighty-seven patients received PCEA. No significant difference of NRS in MA and PCEA group within 24 hours after surgery either in rest (0.2 ± 1 compared with 0.22 ± 0.98; p = 0.930) or motion (0.40 ± 1.56 compared with 0.31± 1.23; p = 0.764). MA group sustained lesser motor blockade than PCEA (6.45% compared with 22.98%; p = 0.028) beyond 24 hours after surgery. The occurrence of numbness is lower in MA group (18.52%) compared with PCEA group(43.33%) (p=0.031). No statistic difference of PONV and dizziness is noted between two groups. However, there is a trend that lesser PONV and dizziness occurred in MA group than PCEA group. Conclusion. TKA patients receiving either MA or PCEA have adequate analgesic efficacy after surgeries. MA group has a lower incidence of motor blockade and PONV than PCEA. This multimodal analgesia proposed here has shown patients' safety and improved pain control after TKA, decreased narcotics use and their associated side effects. Besides, lesser motor blockade and adequate pain relief may encourage patient's early rehabilitation

Background. Narcotics are commonly prescribed for pain control of orthopedic trauma but injury pattern and severity, in addition to patient factors, result in varying dosing requirements. These factors, coupled with increasing pressure to reduce narcotic consumption, highlight the importance of narcotic stewardship and comprehension of patient factors leading to higher pain control demands. The purpose of this study is to understand whether or not narcotic consumption is greater in patients who present to the emergency department with positive drug screen (utox) for illicit substances. Methods. We performed a retrospective chart review of 300 consecutive trauma activations during the 2015 calendar year. Of the patient cohort, 226 patients received a utox screen which represents the cohort for this study. Utox screen included amphetamines, barbiturates, benzodiazepines, cocaine, ethanol, methadone, phencyclidine, and tetrahydrocannabinol. Opioids given hospital stay were converted to oral morphine equivalents using ratios available in the current literature. The average daily equivalent was calculated for their total hospital stay and recorded. Patient injury severity score (ISS), age, gender, length of stay, readmission rates were also recorded. Statistical comparisons were made using SPSS version 23 (IBM, Aramonk, NY). Data distributions were examined with the Shapiro-Wilk test of normality between group comparisons were made with Mann Whitney U tests. Chi squared test was used to evaluate categorical data. Significance was set at p=0.05. Results. There were 108 (48%) positive utox tests of the 226 that received a utox test. There was no difference in gender distribution or age between the 2 groups. The calculated morphine equivalent consumption of the positive utox patient cohort was compared against the negative utox group. The median daily oral morphine equivalents in the positive utox group was 23.85 versus 12.05 for those with a negative utox screen. This was found to be statistically significant with a p value of 0.014. The average length of stay for the positive utox group was 3 days versus 2 days for the negative utox group. This also was statistically significant with a p value of 0.009. There was no statistical significance for ISS (5 in utox positive versus 5 in utox negative patients) nor was there any significance found in the rate of readmissions. Discussion. Our study shows that infividuals found to have positive utox screening for illicit drug use require more opioids for pain control and have longer hospital stays. These increased resource requirements exist despite no statistically significant difference in ISS. The high rate of positive findings and differences in patient clinical course support continued utox screening in trauma activation patients. When treating these patients, physicians should be aware of potential differences in pain management strategies and would likely benefit from multimodal pain control progam

More than half of patients with neck of femur (NOF) fractures report their pain as severe to very severe in the first 24hrs. Opioids remain the most commonly used analgesia and are effective for static pain but not dynamic pain. Opioids provide suboptimal analgesia when patients are in a dynamic transition state and their side-effects are a source of morbidity in these patients. The Fascia Iliaca Compartment Block (FICB) involves infiltration of the fascia iliaca compartment with a large volume of low concentrated local anaesthetic to reduce pain by affecting the femoral and lateral cutaneous nerve of the thigh. The London Quality Standards for Fractured neck of femur services (2013) stated that the FICB should be routinely offered to patients. We performed an audit of patient outcomes following the introduction of the FICB across three centres. We performed a two-cycle audit across two hospitals in 2014/15. The first cycle audited compliance with the NICE guidance in the management and documentation of pain and AMTS (Abbreviated Mental Test Scores) in patients. The second cycle was conducted following the integration of the FICB into the multidisciplinary NOF fracture protocol across three hospital sites. Data was collected on numeric pain scores, pre and post-op AMTS and opioid requirements. There were 40 patients audited with 20 in the first cycle prior to the introduction of the FICB and 20 following this. In the second cycle, there was a statistically significant improvement (p<0.001) in the difference between the pre and post-op AMTS. The preliminary findings in this audit support the use of the FICB adjunct to analgesia in the pre-operative management of NOF fracture patients. The FICB is a safe procedure and the organisational learning of this procedure through a multidisciplinary approach can significantly improve the outcomes of NOF fracture patients

Cancer associated bone pain (CIBP) is a common event in patients with advanced disease with bone metastases (BM), significantly impairing their quality of life. Treatment options are limited and mainly based on the use of opioids with unacceptable side effects. Local acidosis is a well-known cause of pain since it directly stimulates nociceptors that express acid-sensing ion channels and densely innervate bone. In BM, local acidosis derives from osteoclast bone resorption activity and from the acidification by glycolytic tumor cells. Here we speculated that the pH lowering of intratumoral interstitial fluid also promotes nociceptors sensitization and hyperalgesia through the activation of cells of mesenchymal origin in BM microenvironment that might release inflammatory and nociceptive mediators. As a model of breast cancer that can metastatise to the bone we used MDA-MB-231 (MDA), and a subclone with a higher tendency to form osteolytic BM (bmMDA). We evaluated the basal expression of proton pumps/ion transporters by Real-Time PCR (Q-RT-PCR). To evaluate the effect of extracellular acidosis on mesenchymal tumor-associated stroma, we used human osteoblast primary cultures from healthy donors and cancer-associated fibroblasts isolated with specific immunobeads from the tumor biopsies of patient with BM. We exposed the cells to pH 6.8 medium at different time points (between 3 to 24 hours). After the short-term incubation with acidosis, for the expression of and acid-sensing ion channels, inflammatory cytokines and nociceptive mediators that can produce hyperalgesia, we used both a wide screening through a deep-sequencing approach and Q-RT-PCR, and ELISA. Xenograft for osteolytic BM induced by intratibial injection of bmMDA were treated with Omeprazole and monitored for CIBP through several cognitive tests. We found a significantly higher extracellular proton efflux and expression of proton pumps/ion transporters associated with the acid-base balance, the monocarboxylate transporter 4 (MCT4), the carbonic anhydrase (CA9), and the vacuolar ATPase (V-ATPase) V. 1. G. 1. subunit, and V. 0. c subunitin bmMDA, a subclone that is prone to form BM in respect to the parental cell line MDA-MB-231. In mesenchymal stromal cells, osteoblasts and cancer-associated fibroblasts, the incubation with pH 6.8 induced the expression of the achid-sensing ion channels AISC3/ACCN3 and AICS4/ACCN4, as well as of the nociceptive modulators nerve growth factor (NGF), Brain-derived neurotrophic factor (BDNF), and of the inflammatory cytokines interleukin 6 (IL6) and 8 (IL8), and Chemokine (C-C motif) ligand 5 (CCL5). Furthermore, the targeting of V0c subunit to inhibit intratumoral acidification significantly reduced CIBP in mice model of BM. In this study we demonstrated for the first time that, in addition to the direct acid-sensing neuronal stimulation, the acidic microenvironment of BM causes hyperalgesia through the activation of an inflammatory reaction in the tumor-associated mesenchymal stroma at the tumor site, thereby offering as a new target for palliative treatment in advanced cancer

The goals of perioperative management are to relieve pain, achieve early mobilization after surgery, reduce length of hospital stay, and obtain adequate patient satisfaction. Several treatment options combining systemic analgesics and/or regional analgesia with or without opioids are available for postoperative pain; however, a gold standard has not been established although there is a progressive shift towards multimodal approaches to improve analgesia while minimizing opioid-related side effects. EX-TRA-05 (DAVID-ART) was a randomised, double-blind, parallel, pivotal study, evaluating the analgesic efficacy and safety of the innovative oral combination of dexketoprofen/tramadol 25mg/75mg in comparison with the individual components (tramadol given at the higher dose of 100mg) on moderate to severe acute pain after total hip replacement. Repeated doses of study drug were administered every 8 hours and pain intensity (PI) was to be scored according to a 100mm visual analogue scale (VAS) on a programmed e-diary every 2 hours over a 56-hour period (i.e. along 7 repeated doses). A placebo arm was included at the first administration to validate the pain model. Rescue medication, metamizole 500mg, was available during the treatment period. The study primary endpoint was the mean sum of the pain intensity difference values throughout the first 8 hours (SPID. 8. ), which considered the 3 active treatment arms and placebo (ITT population; N=641). In this phase, a clear superiority of the combination over the single agents was demonstrated (p<0.05). An additional analysis was performed during the entire 0–56h repeated-dose period excluding those patients who had received placebo at the first dose (N=161). The estimated mean (SE) differences on PI-VAS over 24, 32 and 56 hours post first dose (0–24h, 0–32h, and 0–56h) between the combination and each single agent were evaluated. Patients who received active analgesic from the first dose (mITT population; N=480) were aged 29–80 years (42% were ≥65 years). At randomisation, pain was moderate (≥40–60mm) in 51% patients and severe (>60mm) in 49%. For dexketoprofen/tramadol, mean (SD) PI-VAS values were 22 (4.0) over 24 hours; 21 (4.1) over 32 hours; and 19 (3.8) over 56 hours. The estimated differences versus dexketoprofen 25mg and tramadol 100mg were respectively 10 (0.7) and 7.6 (0.7) over 24 hours; 9.8 (0.6) and 7.2 (0.6) over 32 hours; and 8.1 (0.5) and 6.3 (0.5) over 56 hours (p<0.0001 for all comparisons), which confirmed the superiority of the combination versus both single agents throughout the periods analysed. This significant higher decrease of PI favouring dexketoprofen/tramadol 25mg/75mg over dexketoprofen 25mg and tramadol 100mg, all given every 8 hours, during the first 56 hours post dose confirmed the superior analgesia shown after the first 0–8h post-dose period. The combination of dexketoprofen/tramadol 25mg/75mg is able to provide a level of analgesia above that achievable by each component alone, with a sustained effect when used as a multiple-dose regimen. The addition of this new combo to the analgesic armamentarium may contribute to facilitate early mobilization after surgery, thus positively impacting perioperative co-morbidities and length of in-hospital stay

Summary. Timing for the application and use of fentanyl patches for pre-emptive analgesia and sedation is crucial to obtain good clinical outcomes. Placement and timing is important to maximise clinical effect and apparent levels of analgesia. Introduction. The use of sheep as preclinical models for the investigation of orthopaedic conditions is gaining momentum, the control of their pain is a significant ethical issue. The daily need for injecting non-steroidal anti-inflammatory drugs (NSAIDs) and/or the shorter acting opioids increases the demand for handling post-operatively which can increase animal distress and risk of human injury. NSAIDs can have a negative effect on bone healing, complicating results. Opioid analgesics have no impact on bone healing. Fentanyl patches have become another option for use in pain management. Pre-emptive analgesia helps reduce the demand on post-operative analgesic use. Fentanyl has the added benefit of producing mild sedation. This study evaluated the pharmacokinetics of fentanyl patches in sheep in an effort to maximise pre and post-surgical analgesia. Methods. Eight sheep were divided into 2 groups of 4. Both groups had a 100µg/kg/hr fentanyl patch (Durogesic – Janssen, Sydney, Australia) applied to the clipped and cleaned skin of the antebrachium and were held in place with a light bandage. (A dose rate range of 1- 1.6µg/kg/hr was achieved). Group 1 had a second patch applied after 72 hours and group 2 had a second patch applied after 24 hours. Blood samples were taken at 0, 3, 6, 12, 24, 36, 48 and 72 hours post patch application. The blood was immediately spun down and the serum drawn off and frozen. Serum levels for fentanyl were measured using commercial ELISA kits and read using a spectrophotometer. Animal behaviour throughout the study was observed and recorded by trained staff (CC, JR). Results. Six hours after the patch application, the sheep were relaxed and easily approachable. They stood calmly while blood was being drawn. This behaviour remained up to the 48 hour time point at which time cornering them in their pen became marginally more difficult, however they still stood calmly for the blood collection. By 72 hours, all sheep co-operation had dissipated. Peak blood levels of Fentanyl were reached by 12 hours post patch application. These levels were maintained with a relatively flat drug plateau for the prescribed 72 hours post application. No difference was found in the peak drug levels post application of the second patch between the two groups. There was no second higher peak in blood levels attained. Discussion. This study quantified the drug absorption and elimination curves of fentanyl using a controlled application method in an effort to better apply and manage post-surgical analgesia in sheep used for orthopaedic studies. The results indicate that the application of fentanyl for pre-emptive surgical analgesia can be applied for the full duration of 72 hours prior to the application of the second patch at the time of surgery. No benefit regarding analgesia appears to be gained from changing the first patch after 24 hours as peak serum levels are not affected. However for peak sedation the second patch can be applied anytime from 6 to 48 hours. This analgesic regime is beneficial to the animal as well as its handling and management