Long-term Opioid Use Research Articles

Sepsis Risk Is Yet Another Reason to Avoid Long-Term Opioid Use

Sepsis Risk Is Yet Another Reason to Avoid Long-Term Opioid Use

Disease-Modifying Antirheumatic Drug Use and Its Effect on Long-term Opioid Use in Patients With Rheumatoid Arthritis.

The prevalence of chronic pain is high in patients with rheumatoid arthritis (RA), increasing the risk for opioid use. The objective of this study was to assess disease-modifying antirheumatic drug (DMARD) use and its effect on long-term opioid use in patients with RA. This cohort study included Medicare beneficiaries with diagnosis of RA who received at least 30-day consecutive prescription of opioids in 2017 (n = 23,608). The patients were grouped into non-DMARD and DMARD users, who were further subdivided into regimens set forth by the American College of Rheumatology. The outcome measured was long-term opioid use in 2018 defined as at least 90-day consecutive prescription of opioids. Dose and duration of opioid use were also assessed. A multivariable model identifying factors associated with non-DMARD use was also performed. Compared with non-DMARD users, the odds of long-term opioid use were significantly lower among DMARD users (odds ratio, 0.89; 95% confidence interval, 0.83-0.95). All regimens except non-tumor necrosis factor biologic + methotrexate were associated with lower odds of long-term opioid use relative to non-DMARD users. The mean total morphine milligram equivalent, morphine milligram equivalent per day, and total days of opioid use were lower among DMARD users compared with non-DMARD users. Older age, male sex, Black race, psychiatric and medical comorbidities, and not being seen by a rheumatologist were significantly associated with non-DMARD use. Disease-modifying antirheumatic drug use was associated with lower odds of long-term opioid use among RA patients with baseline opioid prescription. Factors associated with non-DMARD use represent a window of opportunity for intervention to improve pain-related quality of life in patients living with RA.

Treatment of Medication-Resistant Neuropathic Pain in a Tetraplegic Patient Using Repetitive Transcranial Magnetic Stimulation (rTMS): A case report (P9-6.009)

<h3>Objective:</h3> N/A <h3>Background:</h3> Transcranial magnetic stimulation (TMS) is a non-invasive method of neuromodulation currently FDA-approved for the treatment of depression, but has also shown promising results in treating neuropathic pain. Given the risks of invasive neuromodulation and the dangers of long-term opioid use, especially in the face of an opioid crisis, it is imperative to find an effective treatment with minimal side effects. <h3>Design/Methods:</h3> The patient is a 74-year old tetraplegic Caucasian man who suffers from severe medication-resistant neuropathic pain following a spinal cord injury. TMS treatment was initiated, using a two-part protocol consisting of high-frequency (10 Hz) stimulation of the left dorsolateral prefrontal cortex (DLPFC) followed by low-frequency (5 Hz) stimulation of the primary motor (M1) cortex. Patient received daily treatment for the first week and decreased in frequency as treatment continued. Pain was measured using the Visual Analog Scale and tracked over 13 weeks (currently ongoing). <h3>Results:</h3> Patient’s pain level before beginning treatment was 6.35/10. Within the first week of treatment, his baseline pain level was reduced to 4.19/10. The lowest pain immediately following treatment was 1.9/10, a 70.1% decrease in pain scores. During the initial week of treatments, the patient reported that pain relief lasted for a few hours immediately following treatment. As treatment continued, he reported experiencing progressively longer relief, and also decreased his dosage of opioids due to the pain relief from the rTMS treatment. <h3>Conclusions:</h3> The pain protocol reduced medication-resistant neuropathic pain in our patient, as measured by the Visual Analog Scale as well as a decrease in opioid usage. Analgesic effects were additive with continual treatment. TMS treatment is non-invasive and could be administered without moving the patient from his wheelchair. The significant, lasting decrease in pain reported by the patient supports the need for further clinical studies of combined M1-rTMS and DLPFC-rTMS treatment for neuropathic pain. <b>Disclosure:</b> Miss Li has nothing to disclose. Dr. Kuluva has received personal compensation in the range of $50,000-$99,999 for serving as an officer or member of the Board of Directors for Piedmont Neuroscience Center. Ms. Paras has nothing to disclose. Mr. Mohammad has nothing to disclose.

OA10 Factors associated with long-term opioid use in fibromyalgia patients newly started on an opioid: results from Clinical Practice Research Datalink

Abstract Background/Aims The impact of the opioid epidemic in North America has caused concern in the United Kingdom. Long-term opioid use is associated with several opioid-related harms and adverse outcomes. Fibromyalgia is frequently treated with opioids due to limited therapeutic options. Understanding what factors are associated with long-term opioid use in such patients is the first step in helping to develop targeted interventions for deprescribing. Therefore, the objective of this study was to (i) quantify the proportion of new opioid users with fibromyalgia who become long-term opioid users; and (ii) identify risk factors associated with long-term opioid use in fibromyalgia. Methods A retrospective cohort study was conducted using data from the Clinical Practice Research Datalink (CPRD). CPRD is a national database of electronic health records within primary care, representation of the general population. Fibromyalgia patients without prior cancer who were new opioid users between 01/Jan/2006 and 31/Aug/2021 were included. Long-term opioid use was defined as at least 3 opioid prescriptions issued within a 90-day period, or ≥ 1 opioid prescription lasting at least 90 days, in the first year of follow-up. Logistic regression analysis and a random forest model were used to identify risk factors related to long-term opioid use. Compared to logistic regression, random forest variable importance measures covered both the effects of individual predictor variables as well as multivariate interactions with other predictor variables. In the random forest model, the mean decrease accuracy (MDA) index to measure the variables’ importance was used; the larger the value of the mean decrease accuracy, the more important the variable is. Results Of the 28,552 fibromyalgia patients who were new opioids users, 7,375 (26%) became long-term opioid users in the first year. In the fully adjusted logistic regression model, suicide and self-harm (adjusted odds ratio [aOR]: 1.98, 95% confidence interval (CI): 1.72-2.27, p &amp;lt; 0.001), substance use disorder (aOR: 2.07, 95%CI: 1.62-2.66, p &amp;lt; 0.001), most deprived (Index of Multiple Deprivation (IMD) quintile 5/most deprived, aOR: 1.98, 95%CI: 1.69-2.33, p &amp;lt; 0.001, compared with quintile 1/least deprived), obesity (aOR: very severely obese, OR: 2.35, 95%CI: 1.76-3.18, p &amp;lt; 0.001) and mean daily morphine milligram equivalents (MME) at the initiation (High (120-199 MME/day): aOR: 34.81, 95%CI: 18.00-78.05, p &amp;lt; 0.001 compared to mean daily MME: Low (&amp;lt;50 MME/day)) were associated with higher risk of long-term opioid use. The three most important variables using the random forest model were mean MME/day at initiation (MDA 140), history of suicide and self-harm (MDA 40) and IMD (MDA 30). Conclusion Almost 1 in 4 patients with fibromyalgia starting opioids became a long-term opioid user in this nationally representative dataset within the first year. The dose of initial opioid prescription, high deprivation score, history of suicide and self-harm, substance use disorder and obesity were associated with long-term opioid use. Disclosure M. Feng: None. C. Ramirez Medina: None. Y. Huang: None. D. Jenkins: None. M. Jani: None.

Prognostic factors for chronic post-surgical pain after lung and pleural surgery: a systematic review with meta-analysis, meta-regression and trial sequential analysis.

Chronic post-surgical pain is known to be a common complication of thoracic surgery and has been associated with a lower quality of life, increased healthcare utilisation, substantial direct and indirect costs, and increased long-term use of opioids. This systematic review with meta-analysis aimed to identify and summarise the evidence of all prognostic factors for chronic post-surgical pain after lung and pleural surgery. Electronic databases were searched for retrospective and prospective observational studies as well as randomised controlled trials that included patients undergoing lung or pleural surgery and reported on prognostic factors for chronic post-surgical pain. We included 56 studies resulting in 45 identified prognostic factors, of which 16 were pooled with a meta-analysis. Prognostic factors that increased chronic post-surgical pain risk were as follows: higher postoperative pain intensity (day 1, 0-10 score), mean difference (95%CI) 1.29 (0.62-1.95), p < 0.001; pre-operative pain, odds ratio (95%CI) 2.86 (1.94-4.21), p < 0.001; and longer surgery duration (in minutes), mean difference (95%CI) 12.07 (4.99-19.16), p < 0.001. Prognostic factors that decreased chronic post-surgical pain risk were as follows: intercostal nerve block, odds ratio (95%CI) 0.76 (0.61-0.95) p=0.018 and video-assisted thoracic surgery, 0.54 (0.43-0.66) p < 0.001. Trial sequential analysis was used to adjust for type 1 and type 2 errors of statistical analysis and confirmed adequate power for these prognostic factors. In contrast to other studies, we found that age had no significant effect on chronic post-surgical pain and there was not enough evidence to conclude on sex. Meta-regression did not reveal significant effects of any of the study covariates on the prognostic factors with a significant effect on chronic post-surgical pain. Expressed as grading of recommendations, assessment, development and evaluations criteria, the certainty of evidence was high for pre-operative pain and video-assisted thoracic surgery, moderate for intercostal nerve block and surgery duration and low for postoperative pain intensity. We thus identified actionable factors which can be addressed to attempt to reduce the risk of chronic post-surgical pain after lung surgery.

Impact of social determinants of health on perioperative opioid utilization in patients with lumbar degeneration

BackgroundSocial determinants of health (SDOH), have been demonstrated to significantly impact health outcomes in spine patients. There may be interaction between opioid use and these factors in spine surgical patients. We aimed to evaluate the social determinants of health (SDOH) which are associated with perioperative opioid use among lumbar spine patients. MethodsThis retrospective cohort study included patients undergoing spine surgery for lumbar degeneration in 2019. Opioid use was determined based on prescription records from the electronic medical records. Preoperative opioid users (OU) were compared with opioid-naïve patients regarding SDOH including demographics like age and race, and clinical data such as activity and tobacco use. Demographics and surgical data, including age, comorbidities, surgical invasiveness, and other variables were also collected from the records. Multivariate logistic regression was used for analysis of these factors. ResultsNinety-eight patients were opioid-naïve and 90 used opioids preoperatively. All OU had ≥3 months of use, had more prior spine surgeries (1.07 vs. 0.44, p<.001) and more comorbidities including diabetes, hypertension, and depression (p=.021, 0.043, 0.017). Patients from lower community median income areas, unemployed, or with lower physical capacity (METS<5) were more likely to use opioids preoperatively. Postoperative opioid use was strongly associated with preoperative opioid use, as well as alcohol use, and lower community median income. At one year postoperatively, OU had higher rates of opioid use [72.2% vs. 15.3%, p<.001]. ConclusionsUnemployment, low physical activity level, and lower community median income were associated with preoperative opioid use and longer-term opioid use postoperatively.

Patients’ Perspectives on the Development of Prescription Opioid Use Disorder in Patients with Chronic Non-Cancer Pain

Introduction: In the past decade, prescription opioid use increased exponentially and concomitantly opioid use disorders (OUD) are becoming more common. Several risk factors for developing OUD have been identified, but little is known regarding the patients’ perspective on developing a prescription OUD. Methods: We recruited 25 adults undergoing treatment for prescription OUD. In-depth, semi-structured interviews focussed on experiences with long-term opioid use, knowledge and attitudes regarding opioids, and access to opioids. A directed content analysis was conducted on the transcribed interviews using NVivo. Results: Participants showed that the development of an OUD is affected by various factors which could be grouped into three themes: (1) experiences driving initiation, (2) experiences driving continuation, and (3) experiences with prescription OUD. Besides the need for pain management, the dynamics of patient-provider communication, care coordination, provider vigilance, and environmental support all contributed to the way patients used their opioids. Conclusion: Patients’ experiences illustrate that the first stage of the development of prescription OUD differs from the development of other substance addictions. Negative reinforcement might play a more prominent role in the early phase of prescription opioid use. Patients expressed a lack of guidance, both at the start of use and long-term use, easy access to new prescriptions and a lack of monitoring as main drivers of the development. Poorly controlled pain and subjective stress fuelled continuous opioid use.

MICROSTRUCTURAL ORGANIZATION OF THE SUBMANDULAR GLAND UNDER CONDITIONS OF 5-WEEK OPIOID INFLUENCE

The use of opioids is an effective method of treatment for severe and acute pain; however, when they used inappropriately, in addition to their powerful pain-relieving properties, opioids cause significant side effects. The initial changes in the human body caused by the use of narcotic substances (opiates) are detected in the oral cavity, in particular, in the salivary glands. The earliest manifestations of pathological changes in the oral cavity are caries, stomatitis, gingivitis, periodontitis and xerostomia. Based on the results of our research and the study of the effect of opioids on other organs, we can conclude that long-term use of opioids has a significant negative effect on the structure of the submandibular gland and homeostasis of the oral cavity as a whole. The presence of a number of unsolved questions regarding the problems of structural reconstruction of the salivary glands during the use of narcotic agents, as well as the possibility of selecting the most effective methods of treatment and prevention of salivary gland diseases determined the choice of this research topic.&#x0D; Materials and methods. The research was performed on 15 mature, white, male rats with body weight 200–220 g, aged 4.5–6 months, which were kept under standard conditions at the vivarium of the Danylo Halytsky Lviv National Medical University. Animals were divided into two groups: experimental and control. In the experimental group, animals (10 rats) were daily administered an opioid analgesic (nalbuphine) intramuscularly according to the following schedule: 1st week – 8 mg/kg, 2nd week – 15 mg/kg, 3rd week – 20 mg/kg, 4th week – 25 mg/kg, V week – 30 mg/kg. Controls were 5 rats that were injected with 0.9% sodium chloride solution in a volume of 1 ml for 5 weeks. We used the histological method to conduct the research.&#x0D; Results. Damage to the organs of the oral cavity and the submandibular gland, in particular, is an element of comorbid pathology caused by long-term use of opioids. During the 5-week administration of the opioid, we observed irreversible destructive changes in the structural organization of the submandibular gland, which was characterized by the dilation of the vessels of the microcirculation, dystrophic and necrotic changes of the final serous and mucous secretory acini, necrosis of serocytes. Such pathological processes in the structural organization of the submandibular gland can cause an imbalance in the quantitative and qualitative composition of saliva and, as a result, a violation of the homeostasis of the oral cavity and the upper parts of the gastrointestinal tract.&#x0D; Conclusions. The results of the research demonstrate the negative impact of long-term opioid exposure on the structural organization of the submandibular gland and are similar to changes in other organs and body systems during long-term opioid exposure. The damage to microcirculation vessels is the starting and primary mechanisms in this process with the subsequent increase of irreversible destructive changes of the submandibular gland. The data of the scientific work have a wide practical and theoretical significance for morphologists, pathomorphologists and dentists in the aspect of developing new methods of diagnosis, prevention and treatment of salivary gland pathology in patients with opiomania and make it possible to establish safe terms of use of «nalbuphine».

Long-term Outcomes Following a Comprehensive Quality Assurance and Process Improvement Endeavor to Minimize Opioid Use After Kidney Transplant

Opioid use following kidney transplant is associated with an increased risk of graft loss and mortality. Opioid minimization strategies and protocols have shown reductions in short-term opioid use after kidney transplant. To evaluate the long-term outcomes associated with an opioid minimization protocol following kidney transplant. This single-center quality improvement study evaluated postoperative and long-term opioid use before and after the implementation of a multidisciplinary, multimodal pain regimen and education process in adult kidney graft recipients from August 1, 2017, through June 30, 2020. Patient data were collected from a retrospective chart review. Preprotocol and postprotocol implementation use of opioids. Between November 7 and 23, 2022, opioid use before and after protocol implementation was evaluated up to 1 year after transplant using multivariable linear and logistic regression. A total of 743 patients were included, with 245 patients in the preprotocol group (39.2% female and 60.8% male; mean [SD] age, 52.8 [13.1 years]) vs 498 in the postprotocol group (45.4% female and 54.6% male; mean [SD] age, 52.4 [12.9 years]). The total morphine milligram equivalents (MME) in the 1-year follow-up in the preprotocol group was 1203.7 vs 581.9 in the postprotocol group. In the postprotocol group, 313 patients (62.9%) had 0 MME in the 1-year follow-up vs 7 (2.9%) in the preprotocol group (odds ratio [OR], 57.52; 95% CI, 26.55-124.65). Patients in the postprotocol group had 99% lower odds of filling more than 100 MME in the 1-year follow-up (adjusted OR, 0.01; 95% CI, 0.01-0.02; P < .001). Opioid-naive patients postprotocol were one-half as likely to become long-term opioid users vs preprotocol (OR, 0.44; 95% CI, 0.20-0.98; P = .04). The study's findings show a significant reduction in opioid use in kidney graft recipients associated with the implementation of a multimodal opioid-sparing pain protocol.

Surgical Approach Does Not Affect Chronic Opioid Usage After Total Hip Arthroplasty

BackgroundThree different surgical approaches (the direct anterior, antero-lateral, and posterior) are commonly used for total hip arthroplasty (THA). Due to an internervous and intermuscular approach, the direct anterior approach may result in less postoperative pain and opioid use, although all 3 approaches have similar outcomes 5 years after surgery. Perioperative opioid medication consumption poses a dose-dependent risk of long-term opioid use. We hypothesized that the direct anterior approach is associated with less opioid usage over 180 days after surgery than the antero-lateral or posterior approaches. MethodsA retrospective cohort study was performed including 508 patients (192 direct anterior, 207 antero-lateral, and 109 posterior approaches). Patient demographics and surgical characteristics were identified from the medical records. The state prescription database was used to determine opioid use 90 days before and 1 year after THA. Regression analyses controlling for sex, race, age, and body mass index were used to determine the effect of surgical approach on opioid use over 180 days after surgery. ResultsNo difference was seen in the proportion of long-term opioid users based on approach (P = .78). There was no significant difference in the distribution of opioid prescriptions filled between surgical approach groups in the year after surgery (P = .35). Not taking opioids 90 days prior to surgery, regardless of approach, was associated with a 78% decrease in the odds of becoming a chronic opioid user (P < .0001). ConclusionOpioid use prior to surgery, rather than THA surgical approach, was associated with chronic opioid consumption following THA.

Perioperative pain management in opioid tolerant and opioid use disorder patients: Considerations for the foot and ankle surgeon

Perioperative management of patients with long term use of opioids has become an increasing challenge. Complicating the care of these patients are the misconceptions regarding opioid prescribing in the opioid-tolerant community and those on maintenance therapy. Healthcare providers receive limited education on pain management including multimodal pain control. Perioperative considerations should be examined. Prescribers are encouraged to consider utilizing a multi-modal regimen in this population. This review aims to better educate the foot and ankle surgeon with up-to-date knowledge in working with the opioid-tolerant patient population. A comprehensive literature review was performed, focusing on perioperative pain management in opioid tolerant patients. Expert opinions and material in this review is provided by a board-certified Addiction Medicine Specialist and board-certified Foot and Ankle Surgeon at a level one trauma center. Pain control in the opioid-tolerant patient population can be challenging for the Foot and Ankle surgeon. Pre-operatively, patients' risk factors for chronic opioid use should be assessed through screening tools. Intra-operatively, sound dialogue between the surgeon and anesthesiologist is imperative with new and emerging techniques. Postoperatively opioid-tolerant patients should resume preoperative dosing of opioids at a minimum. A multimodal pain regimen is associated with superior pain relief and decreased opioid consumption. Patients on maintenance therapy including Methadone, and Buprenorphine should continue these medications during the perioperative period. These patients may benefit from an addiction medicine consultation for more comprehensive care.

Incidence of opioid-induced esophageal dysfunction.

Retrospective studies have suggested that long-term use of opioids can cause esophageal motility dysfunction. A recent clinical entity known as opioid-induced esophageal dysfunction (OIED) has been postulated. There is no data from prospective studies assessing the incidence of opioid-induced effects on the esophagus. Evaluate the incidence of OIED during chronic opioid therapy. From February 2017 to August 2018, all patients seen in the Pain Unit of the hospital, who started opioid treatment for chronic non-neoplastic pain and who did not present esophageal symptoms previously, were included. The presence of esophageal symptoms was assessed using the Eckardt score after 3 months and 1 year since the start of the study. In February 2021, the clinical records of all included patients were reviewed to assess whether esophageal symptoms were present and whether opioid therapy was continued. In patients presenting with esophageal symptoms, an endoscopy was performed and, if normal, a high-resolution esophageal manometry was performed. For a confidence level of 95%, a 4% margin of error and an estimated prevalence of 4%, a sample size of 92 patients was calculated. 100 patients were included and followed while taking opioids, for a median of 31 months with a range between 4 and 48 months. Three women presented with dysphagia during the first 3 months of treatment, being diagnosed with esophagogastric junction outflow obstruction; type II and type III achalasia. The cumulative incidence of OIED was 3%; 95%-CI: 0-6%. Chronic opioid therapy in patients with chronic non-neoplastic pain is associated with symptomatic esophageal dysfunction.

A multi-disciplinary program for opioid sparse arthroplasty results in reduced long-term opioid consumption: a four year prospective study

IntroductionThe current opioid epidemic poses patient safety and economic burdens to healthcare systems worldwide. Postoperative prescriptions of opioids contribute, with reported opioid prescription rates following arthroplasty as high as 89%. In this multi-centre prospective study, an opioid sparing protocol was implemented for patients undergoing knee or hip arthroplasty. The primary outcome is to report our patient outcomes in the context of this protocol, and to examine the rate of opioid prescription on discharge from our hospitals following joint arthroplasty surgery. This is possibly associated with the efficacy of the newly implemented Arthroplasty Patient Care Protocol.MethodsOver three years, patients underwent perioperative education with the expectation to be opioid-free after surgery. Intraoperative regional analgesia, early postoperative mobilisation and multimodal analgesia were mandatory. Long-term opioid medication use was monitored and PROMs (Oxford Knee/Hip Score (OKS/OHS), EQ-5D-5 L) were evaluated pre-operatively, and at 6 weeks, 6 months and 1 year postoperatively. Primary and secondary outcomes were opiate use and PROMs at different time points.ResultsA total of 1,444 patients participated. Two (0.2%) knee patients used opioids to one year. Zero hip patients used opioids postoperatively at any time point after six weeks (p < 0.0001). The OKS and EQ-5D-5 L both improved for knee patients from 16 (12–22) pre-operatively to 35 (27–43) at 1 year postoperatively, and 70 (60–80) preoperatively to 80 (70–90) at 1 year postoperatively (p < 0.0001). The OHS and EQ-5D-5 L both improved for hip patients from 12 (8–19) preoperatively to 44 (36–47) at 1 year postoperatively, and 65 (50–75) preoperatively to 85 (75–90) at 1 year postoperatively (p < 0.0001). Satisfaction improved between all pre- and postoperative time points for both knee and hip patients (p < 0.0001).ConclusionsKnee and hip arthroplasty patients receiving a peri-operative education program can effectively and satisfactorily be managed without long-term opioids when coupled with multimodal perioperative management, making this a valuable approach to reduce chronic opioid use.

Return Rates for Opioid versus Nonopioid Management of Patients with Abdominal Pain in the Emergency Department

BackgroundResearch suggests that opioid treatment for abdominal pain, which comprises a large proportion of patients presenting to the emergency department (ED), may contribute to long-term opioid use without significant benefits with regard to symptom management. ObjectivesThis study seeks to assess the association between opioid use for management of abdominal pain in the ED and return ED visits for abdominal pain within 30 days for patients discharged from the ED at initial presentation. MethodsWe conducted a retrospective, multicenter observational study of adult patients presenting to and discharged from 21 EDs with a chief concern of abdominal pain between November 2018 and April 2020. The proportion of 30-day return visits to the ED for patients who received opioid analgesics was compared with a reference group of patients who only received acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), or both. ResultsOf the 4745 patients, 1304 (27.5%) received opioids and 1101 (23.2%) only received either acetaminophen, NSAIDs, or both. Among those given opioids, 287 (22.0%) returned to the ED for abdominal pain within 30 days, compared with 162 (14.7%) of those in the reference group (odds ratio 1.57, 95% confidence interval 1.27–1.95, p-value < 0.001). ConclusionPatients given opioids for abdominal pain in the ED had 57% increased odds of a return ED visit within 30 days compared with those given only acetaminophen or NSAIDs. This warrants further research on the use of nonopioid analgesics in the ED, especially in patients with anticipated discharge.

Interdisciplinary strategies to prevent long-term and detrimental opioid use following trauma: a stakeholder consensus study.

Prolonged opioid use is common following traumatic injuries. Although preventive strategies have been recommended, the evidence supporting their use is low. The objectives of this study were to select interdisciplinary strategies to prevent long-term, detrimental opioid use in trauma patients for further evaluation and to identify implementation considerations. A consensus study using the nominal group technique. Four trauma systems in Canada. Participants included expert clinicians and decision makers, and people with lived experience. Participants had to discuss the relevance and implementation of 15 strategies and then rank them using a 7-point Likert scale. Implementation considerations were identified through a synthesis of discussions. A total of 41 expert stakeholders formed the nominal groups. Overall, eight strategies were favored: 1) using multimodal approach for pain management, 2) professional follow-up in physical health, 3) assessment of risk factors for opioid misuse, 4) physical stimulation, 5) downward adjustment of opioids based on patient recovery, 6) educational intervention for patients, 7) training offered to professionals on how to prescribe opioids, and 8) optimizing communication between professionals working in different settings. Discussions with expert stakeholders revealed the rationale for the selected strategies and identified issues to consider when implementing them. This stakeholder consensus study identified, for further scientific study, a set of interdisciplinary strategies to promote appropriate opioid use following traumatic injuries. These strategies could ultimately decrease the burden associated with long-term opioid use.

Trends and correlates of concurrent opioid and benzodiazepine and/or gabapentinoid use among Ontario nursing home residents.

A concern with long-term opioid use is the increased risk arising when opioids are used concurrently with drugs that can potentiate their associated adverse effects. The drugs most often encountered are benzodiazepines (BZDs) and gabapentinoids. Our study objectives were to examine trends in the concurrent use of opioids and BZDs, or gabapentinoids, in a Canadian nursing home population over an 11-year period, and current resident-level correlates of this concurrent use. We conducted a population-based, repeated cross-sectional study among Ontario nursing home residents (>65 years) dispensed opioids between April 2009 and February 2020. For the last study year, we examined cross-sectional associations between resident characteristics and concurrent use of opioids with BZDs or gabapentinoids. Linked data on nursing home residents from clinical and health administrative databases was used. The yearly proportions of residents who were dispensed an opioid concurrently with a BZD or gabapentinoid were plotted with percent change derived from log-binomial regression models. Separate modified Poisson regression models estimated resident-level correlates of concurrent use of opioids with BZDs or gabapentinoids. Over the study period, among residents dispensed an opioid there was a 53.2% relative decrease (30.7% to 14.4%) in concurrent BZD and a 505.4% relative increase (4.4% to 26.6%) in concurrent gabapentinoid use. In adjusted models, increasing age and worsening cognition were inversely associated with the concurrent use of both classes, but most other significantly related covariates were unique to each drug class (e.g., sex and anxiety disorders for BZD, pain severity and presence of pain-related conditions for gabapentinoids). Co-administration of BZDs or gabapentinoids in Ontario nursing home residents dispensed opioids remains common, but the pattern of co-use has changed over time. Observed covariates of concurrent use in 2019/20 suggest distinct but overlapping resident populations requiring consideration of the relative risks versus benefits of this co-use and monitoring for potential harm.

A277 A NOVEL PH-SENSITIVE Μ-OPIOID RECEPTOR AGONIST THAT DOES NOT INDUCE TOLERANCE IN A COLITIS MOUSE MODEL

Abstract Background Adequate pain control in inflammatory bowel disease (IBD) can require opioids due to their high analgesic potency. The long-term use of opioids, however, is limited by the development of tolerance. This leads to reduced analgesic efficacy over time, resulting in escalating opioid dosing and thus increased risk of serious side effects. We previously demonstrated the safety and effectiveness of a novel pH-sensitive µ-opioid receptor (MOR) agonist, NFEPP, in a murine colitis pain model, but its tolerance potential with chronic administration is unknown. Purpose To assess the tolerance potential of NFEPP compared to its parent compound fentanyl during acute colitis in a preclinical mouse model. Method Acute colitis in C57BL/6 mice was induced using 2.5% dextran sulphate sodium for 5 days. NFEPP or fentanyl were then administered s.c. every 4 hours between 7am and 11pm over 5 days in daily increasing concentrations (0.4-1.5 mg/kg/d). Analgesic tolerance to opioids was assessed in conscious mice by measuring visceromotor responses (VMRs) to noxious colorectal distensions. Tolerance to the MOR agonist DAMGO in NFEPP or fentanyl treated mice was evaluated using patch-clamp recordings from dorsal root ganglion (DRG) neurons and extracellular recordings from lumbar splanchnic nerves that innervate the colon. Inflammation was assessed by macroscopic analyses, histological scoring and tissue-pH measurements of the inflamed colon. Group differences were analyzed using two-way ANOVA with Bonferroni′s or Tukey′s post-test (p-value &amp;lt;0.05). Result(s) NFEPP significantly reduced VMRs before and after chronic NFEPP treatment (39% reduction, p&amp;lt;0.05 vs. 41% reduction, p&amp;lt;0.05, compared to baseline at 80 µl). No differences of NFEPP induced antinociceptive actions were observed comparing VMR measurements before and after chronic administration (p=0.44). However, the analgesic activity of fentanyl decreased over time with less VMR inhibition observed after chronic treatment compared to fentanyl naïve mice (p&amp;lt;0.05). Cross tolerance testing between these two opioids revealed a loss of NFEPP- induced VMR inhibition in fentanyl treated mice, but fentanyl effects in the NFEPP treatment group remained unchanged. In patch-clamp recordings, DAMGO (100nM) evoked antinociceptive actions in DRG neurons from NFEPP treated mice (rheobase increase: 50%, p&amp;lt;0.05, compared to vehicle) whereas no change in rheobase with DAMGO was observed in DRG neurons from fentanyl treated mice. Afferent nerve activity from lumbar splanchnic nerves in response to von Frey filament probing decreased after DAMGO (100nM) application in NFEPP treated mice (p&amp;lt;0.05, compared to control probing), but showed no change in fentanyl treated mice. Colonic length, diameter, histological damage and tissue-pH did not differ between the two opioid treatment groups. Conclusion(s) Chronic administration of NFEPP during acute murine colitis does not lead to analgesic tolerance within the visceral nociceptive system, in contrast to its parent compound fentanyl. Please acknowledge all funding agencies by checking the applicable boxes below CCC Disclosure of Interest None Declared

A State-of-the-Art Review on Opioids Induced Constipation and its Management

Background: Pain is a complex physiological and psychological response to a noxious stimulus, sometimes deteriorating a patient’s quality of life. Opioids remain the mainstay treatment modality for chronic pain. Several concerns are raised regarding the long-term use of opioids and the risks associated with their usage. Findings advocate that the longstanding practice of opioid consumption manifests in adverse effects. Objective: Due to the physiological changes opioids instigate in the gastrointestinal tract, opioid-induced constipation remains a common complication pragmatic in patients undergoing opioid medications. Several therapeutic interventions are made available, and the review describes the overall medications with practical examples, aiding in selecting a treatment plan. Methods: The method comprises data collection from various search engines like PubMed, ScienceDirect, and SciFinder to get coverage of relevant literature for accumulating appropriate information regarding pain management, opioids, opioid-induced constipation, and its pharmacological interventions. Results: The thoughtful custom of exploring several options to manage opioid-induced constipation must allow patients to benefit from opioid analgesia. Conclusion: This paper reviews the role of opioids in pain management, underlying mechanisms of their action, opioid-induced constipation, and pharmacological therapies, with experimental studies aiding clinicians to optimise treatment plans.

Out-of-hospital opioid prescriptions after knee and hip arthroplasty: prescribers and the first prescribed opioid

BackgroundWe determined the first prescribed opioid and the prescribers of opioids after knee and hip arthroplasty (KA/HA) between 2013 and 2018 in the Netherlands. We also evaluated whether the first prescribed opioid dose was associated with the total dispensed dose and long-term opioid use in the first postoperative year. MethodsThe Dutch Foundation for Pharmaceutical Statistics was linked to the Dutch Arthroplasty Register. Stratified for KA/HA, the first out-of-hospital opioid within 30 days of operation was quantified as median morphine milligram equivalent (MME). Opioid prescribers were orthopaedic surgeons, general practitioners, rheumatologists, anaesthesiologists, and other physicians. Long-term use was defined as ≥1 opioid prescription for >90 postoperative days. We used linear and logistic regression analyses adjusted for confounders. ResultsSeventy percent of 46 106 KAs and 51% of the 42 893 HAs were prescribed ≥1 opioid. Oxycodone increased as first prescribed opioid (from 44% to 85%) whereas tramadol decreased (64–11%), but their dosage remained stable (stronger opioids were preferred by prescribers). An increase in the first prescription of 1% MME resulted in a 0.43%/0.37% increase in total MME (KA/HA, respectively). A 100 MME increase in dose of the first dispensed opioid had a small effect on long-term use (prevalence: 25% KA, 20% HA) (odds ratio=1.02/1.01 for KA/HA, respectively). Orthopaedic surgeons increasingly prescribed the first prescription between 2013 and 2018 (44–69%). General practitioners mostly prescribed consecutive prescriptions (>50%). ConclusionOxycodone increased as first out-of-hospital prescription between 2013 and 2018. The dose of the first prescribed opioid was associated with the total dose and a small increased risk of prolonged use. First prescriptions were mostly written by orthopaedic surgeons and consecutive prescriptions by general practitioners.

A Closer Look at Opioid-Induced Adrenal Insufficiency: A Narrative Review

Among several opioid-associated endocrinopathies, opioid-associated adrenal insufficiency (OIAI) is both common and not well understood by most clinicians, particularly those outside of endocrine specialization. OIAI is secondary to long-term opioid use and differs from primary adrenal insufficiency. Beyond chronic opioid use, risk factors for OIAI are not well known. OIAI can be diagnosed by a variety of tests, such as the morning cortisol test, but cutoff values are not well established and it is estimated that only about 10% of patients with OIAI will ever be properly diagnosed. This may be dangerous, as OIAI can lead to a potentially life-threatening adrenal crisis. OIAI can be treated and for patients who must continue opioid therapy, it can be clinically managed. OIAI resolves with opioid cessation. Better guidance for diagnosis and treatment is urgently needed, particularly in light of the fact that 5% of the United States population has a prescription for chronic opioid therapy.