Long-acting Opioids Research Articles

Long-acting Opioid Use and the Risk of Serious Infections: A Retrospective Cohort Study.

Although evidence from animal and human studies indicates opioid analgesics increase susceptibility to infections, it is unclear whether the risk varies by specific opioid. We compared the risk of serious infection among patients initiating long-acting opioid analgesics with and without previously reported immunosuppressive properties. We conducted a retrospective cohort study of Tennessee Medicaid enrollees age ≥18 years initiating long-acting opioids (1995-2015). Hospitalizations for serious infection were identified using validated coding algorithms. We used multivariable Poisson regression models to calculate adjusted incidence rate ratios (aIRR) and 95% confidence intervals (CI) to compare the infection risk among patients using long-acting opioids with known immunosuppressive properties (morphine, fentanyl, methadone) to the infection risk among patients using long-acting opioids without known immunosuppressive properties (oxycodone, oxymorphone, tramadol) accounting for demographics, opioid dose, comorbidities and pain conditions, medication use, frailty indicators, and healthcare encounter history using exposure propensity scores. We further compared users of individual long-acting opioids to long-acting morphine users (considered the prototypical immunosuppressive opioid). Among the 61 240 patients initiating opioids with immunosuppressive properties and 22 811 patients initiating opioids without immunosuppressive properties, we identified 1906 serious infections. Nonimmunosuppressive opioid users had a lower rate of infections than immunosuppressive opioid users (aIRR:0.78 [CI: 0.66-0.91]). Among individual opioids, oxycodone users had a lower rate of infection than morphine users (aIRR:0.73 [CI: 0.60-0.89]). There were no significant differences in the infection risk between other opioids and morphine. The risk of serious infections among long-acting opioid users varies by opioid type. Providers should carefully consider the risk of serious infections when making pain management decisions.

Readiness and recovery: Transferring between methadone and buprenorphine/naloxone for the treatment of opioid use disorder.

Long-acting opioids are prescribed as part of treatment for opioid use disorders; methadone and buprenorphine are well researched and commonly prescribed for the treatment of opioid use disorder. Meta-analysis suggests that buprenorphine has a slightly poorer retention rate in treatment as compared to methadone. Benefits of buprenorphine/naloxone include greater ease in ceasing treatment and less use of illicit opioids while in treatment as compared to methadone. There are a number of qualitative and mixed-method studies that ask patients about their experiences of methadone maintenance and buprenorphine maintenance treatment. This research aimed to understand perspectives of receiving buprenorphine/naloxone for the treatment of opioid use disorder. A qualitative descriptive approach was used. Seven participants with a current diagnosis of opioid use disorder treated with buprenorphine/naloxone were interviewed. Thematic analysis extracted four themes: drivers for opioid substitution treatment change; readiness for buprenorphine/naloxone substitution treatment; absence of effect from buprenorphine/naloxone; and an increased sense of citizenship on buprenorphine/naloxone. This study identified a number of factors influencing participants' decision-making in transferring between methadone and buprenorphine/naloxone for the treatment of their opioid use disorder. Methadone was preferred by those seeking sedation and wishing to continue using other opioids, and buprenorphine/naloxone was most effective for participants no longer wishing to experience sedation and seeing opioid abstinence as an end point in their recovery. Changing treatment expectations are important to consider when determining medication selection and highlight the importance of quality information when determining the most suitable medication for the treatment of opioid use disorder.

The Opioid Crisis and the Orthopedic Surgeon

Opioid use and abuse has become a national crisis in the United States. Many opioid abusers become addicted through an initial course of legal, physician-prescribed medications. Consequently, there has been increased pressure on medical care providers to be better stewards of these medications. In orthopedic surgery and total joint arthroplasty, pain control after surgery is critical for restoring mobility and maintaining patient satisfaction in the early postoperative period. Before the opioid misuse epidemic, orthopedic surgeons were frequently influenced to “treat pain with pain medications.” Long-acting opioids, such as OxyContin were used commonly. In the past decade, there has been a paradigm shift in favor of multimodal pain control with limited opioid use. This review will discuss 4 major topics. First, we will describe the pressures on orthopedic surgeons to prescribe narcotic pain medications. We will then discuss the major and minor complications and side effects associated with these prescriptions. Second, we will review how these factors motivated the development of alternative pain management strategies and a multimodal approach. Third, we will look at perioperative interventions that can reduce postoperative opioid consumption, including wound injections and peripheral nerve blocks, which have shown superb clinical results. Finally, we will recommend an evidence-based program that avoids parenteral narcotics and facilitates rapid discharge home without readmissions for pain-related complaints.

Learning optimal opioid prescribing and monitoring: a simulation study of medical residents.

ObjectiveHospitalized patients often receive opioids. There is a lack of consensus regarding evidence-based guidelines or training programs for effective management of pain in the hospital. We investigated the viability of using an Internet-based opioid dosing simulator to teach residents appropriate use of opioids to treat and manage acute pain.Materials and methodsWe used a prospective, longitudinal design to evaluate the effects of simulator training. In face-to-face didactic sessions, we taught 120 (108 internal medicine and 12 family medicine) residents principles of pain management and how to use the simulator. Each trainee completed 10 training and, subsequently, 5 testing trials on the simulator. For each trial, we collected medications, doses, routes and times of administration, pain scores, and a summary score. We used mixed-effects regression models to assess the impact of simulation training on simulation performance scores, variability in pain score trajectories, appropriate use of short- and long-acting opioids, and use of naloxone.ResultsTrainees completed 1582 simulation trials (M = 13.2, SD = 6.8), with sustained improvements in their simulated pain management practices. Over time, trainees improved their overall simulated pain management scores (b = 0.05, P < .01), generated lower pain score trajectories with less variability (b = −0.02, P < .01), switched more rapidly from short-acting to long-acting agents (b = −0.50, P < .01), and used naloxone less often (b = −0.10, P < .01).Discussion and conclusionsTrainees translated their understanding of didactically presented principles of pain management to their performance on simulated patient cases. Simulation-based training presents an opportunity for improving opioid-based inpatient acute pain management.

Practices, Attitudes, and Beliefs of Palliative Care Physicians Regarding the Use of Methadone and Other Long-Acting Opioids in Children with Advanced Cancer.

Palliative care physicians often assist with pain management in children with cancer, but little is known about how they use long-acting opioids for chronic pain with these patients. To determine the practices, attitudes, and beliefs of palliative care physicians toward the use of long-acting opioids in children with advanced cancer. An electronic survey was sent to all members of The American Academy of Pediatrics (AAP) Section of Hospice and Palliative Medicine (SOHPM) and those identified as physicians who provide palliative care to children on the AAP SOHPM LISTSERV®. The response rate to the survey was 62% (116/188). A majority (66% [77/116]) of physicians are board certified in both pediatrics and hospice and palliative medicine. This represents 28% of all board-certified pediatric palliative care physicians. Most palliative care physicians report comfort in using long-acting opioids in children (84-94%), with the exception of long-acting hydromorphone (37%). Physicians perceived methadone as least costly (3%) but associated it with a higher perceived family resistance (51%). As compared with pediatric palliative care fellowship-trained physicians, nonpediatric fellowship-trained physicians perceived titration of oxycodone ER and morphine ER to be easier (p = 0.06, p = 0.07) and less likely to agree that the main reason for starting methadone is that the existing formulations of other long-acting opioids are unsuitable for children (p = 0.05). Most physicians who provide palliative care to children are comfortable using opioids but there is significant variation in the level of comfort with different opioids. This information will be helpful in developing targeted education for palliative care providers.

Opioid tolerance and clinically recognized opioid poisoning among patients prescribed extended-release long-acting opioids.

In recognition of potential for increased overdose risk, drug labels for extended-release and long-acting (ER/LA) opioids emphasize the need for established opioid tolerance prior to initiating high dosages. Describe the proportion of patients with opioid tolerance prior to initiation of 90 morphine milligram equivalents (MME) ER/LA opioids and examine subsequent risk of opioid poisoning. We used Truven Health Analytics' MarketScan Databases (2006-2015) to identify patients initiating ER/LA opioids ≥90 MME. We examined prescription histories and describe the proportion of initiators with opioid tolerance (defined as ≥7days of 60 MME in the prior 14days). We adjusted for age, sex, year of initiation, and baseline comorbidities using inverse probability of treatment weighted Cox proportional hazards models. We estimated adjusted hazard ratios and 95% confidence intervals for the effect of opioid tolerance on the risk of clinically recognized opioid poisoning (based on diagnosis codes) in specific periods (0-7, 8-30, 31-90, and 91-365days) following initiation. Among 372038 initiators, 38% did not meet opioid tolerance criteria. The proportion of nontolerant initiators was highest among those initiating methadone (44%) and fentanyl (42%). Nontolerant patients were 37% more likely to be diagnosed with opioid poisoning (adjusted hazard ratios=1.37 [1.07, 1.76]) in the week following ER/LA initiation. Over one-third of patients initiating ≥90 MME ER/LA opioids did not have evidence of opioid tolerance. The 7days following high dose ER/LA initiation may represent a high-risk period for clinically diagnosed opioid poisoning in patients who do not have prior opioid tolerance.

Evaluating the early impacts of delisting high-strength opioids on patterns of prescribing in Ontario.

Ontario delisted high-strength fentanyl, hydromorphone and morphine from the public drug formulary for non-palliative care prescribers on 31 January, 2017. Our aim is to assess the early impact of this policy on prescribing patterns and to examine whether this impact varied by prescriber type, opioid type and opioid strength. We conducted a population-based, cross-sectional study on palliative and non-palliative care patients dispensed fentanyl, hydromorphone or morphine through the Ontario public drug program between 1 January, 2014, and 31 July, 2017. For each month during the study period, we reported the total number of high-strength opioid recipients stratified by prescriber type, and the total volume of each drug dispensed, stratified by strength. We used interventional autoregressive integrated moving average (ARIMA) models to assess the policy's impact on prescribing patterns. We observed a 98% decrease in the total number of publicly funded recipients of high-strength opioids between December 2016 and July 2017 (5930 to 133 recipients) for all prescribers. The policy led to a significant decline in the total volume of all three opioids dispensed: hydromorphone from 20 374 621 to 16 952 097 mg (p < .01); morphine from 40 644 190 to 33 555 480 mg (p < .03); and fentanyl from 9 604 913 to 5 842 405 mcg/h (p < .01). For both fentanyl and hydromorphone, this reduction generally corresponded to an increase in the number of low-strength opioids dispensed. Delisting high-strength opioids substantially reduced the number of highstrength opioid recipients and reduced the overall volume of long-acting opioids dispensed in Ontario through the public drug program. Future studies should examine its impact on patient outcomes.

Methadone as the Initial Long-Acting Opioid in Children with Advanced Cancer.

Methadone is an attractive medication for treating children with advanced cancer with pain as it is the only long-acting opioid available as a liquid. However, it is not frequently used due to concerns about potential toxicities and side effects. Evaluate the efficacy and safety of methadone as the first long-acting opioid in children with advanced cancer. Retrospective chart review of 52 consecutive patients referred to Pediatric Supportive Care for pain management started on methadone as their first long-acting opioid. Data collected at baseline, follow-up visits #1 (F1) and #2 (F2) included child and parent-reported outcomes for various physical and psychological symptoms, opioid side effects and other clinical data. Symptoms were rated on a 0 (not at all) to 4 (a lot) scale. Pain (mean ± standard deviation [SD]) scored by the child was 3.6 (±0.6)/4 at baseline and 1.8 (±1.1)/4 at F1 (p < 0.0001). Compared to baseline, pain scored by the child at F2 was 1.2 (±1.3)/4 (p < 0.0001). Pain scored by the parent was 3.5 (±0.7)/4 at baseline and 1.4 (±1.3)/4 at F1 (p < 0.0001). Compared to baseline, pain scored by the parent at F2 was 1.0 (±1.2)/4 (p < 0.0001). Thirty-three (70%) patients at F1 and 23 (79%) patients at F2 did not need a change in dose of methadone. No cardiac arrhythmias or opioid neurotoxicity was observed. Initiation of methadone was effective and safe as the first long-acting opioid in children with pain.

Exploring the Multiple Roles of Acupuncture in Alleviating the Opioid Crisis.

Exploring the Multiple Roles of Acupuncture in Alleviating the Opioid Crisis.

Comparison of Opioid Prescribing Among Cancer and Noncancer Patients Aged 18–64: Analysis Using Administrative Data

BackgroundOpioid prescribing has been increasingly scrutinized among noncancer patients. As an unintended consequence, opioids may be underprescribed for cancer patients. The purpose of this study was to compare trends in opioid prescribing in younger adults with and without cancer. MethodsFrom 2004 to 2013, Ontario residents aged 18–64 years eligible for government paid pharmacare were annually stratified into three groups: no cancer history, cancer diagnosis more than five years ago, and cancer diagnosis five years ago and less. We evaluated time trends in two annual outcomes: opioid prescription rate and mean daily opioid dose. ResultsIn 2013, 800,371 individuals were eligible for this study (3% with recent cancer and 2% with remote cancer). Across all years, compared with noncancer patients, overall opioid prescription rates were 43% and 26% higher for those with recent and remote cancer, respectively. Overall, a 1% relative annual increase was seen in those without cancer and a 1% decrease was seen in those with a recent cancer. Changes in prescription rates varied with drug class and cancer group. Notably, long-acting opioids had a relative annual increase of 7% in noncancer patients vs. 2% in recent cancer patients. Immediate-release combination agents had a relative annual decrease of 2% for all cancer groups. Trends in mean daily dose were similar between groups, but by 2013, they were lowest in recent cancer patients, regardless of drug class. InterpretationSecular trends in opioid prescribing affect cancer and noncancer patients similarly. Further research is required to assess the potential impact on symptom management.

Opioid Consumption Following Foot and Ankle Surgery.

Patients undergoing foot/ankle surgery during a 3-month period who met inclusion criteria were surveyed at their first postoperative visit. Information collected included gender, number of prescribed pills remaining, satisfaction with pain control, and willingness to surrender leftover opioids to a Drug Enforcement Administration (DEA) disposal center. Additional data, including utilization of a perioperative nerve block and type (bony versus nonbony) and anatomic region of procedure, were collected through review of the medical record. All data were analyzed in a retrospective fashion. A total of 171 patients with a mean age of 53.1 ± 15.5 years (range, 18-81 years) were included in the study. The mean number of opioids taken was 27.2 ± 17.5 pills (range, 0-70). The mean number of short-acting opioids and long-acting opioids taken was 21.4 ± 14.8 and 9.2 ± 5.0 pills, respectively. Most (73.5%) patients were satisfied with their pain control. Patients who underwent ankle/hindfoot surgery took more long-acting opioids on average than others ( P = .047). There was not a significant difference in opioid usage between bony and nonbony procedures. Of those with leftover opioids, 63% were willing to surrender them to a DEA disposal center. Patients willing to surrender leftover medications had both more short-acting ( P < .001) and long-acting ( P = .015) opioids leftover than those not willing to surrender them. Most patients undergoing foot/ankle surgery had opioids leftover at the first postoperative visit, and most were willing to surrender them. We can adequately treat patients' pain and decrease the number of opioid pills available in the community by decreasing the number of pills prescribed and encouraging disposal of leftovers. Level IV, retrospective case series.

(248) - Profile of the pharmacological approach needed in order to achieve the best pain control in a population of advanced cancer patients

Pain is still a challenging symptom in advanced cancer patients. The World Health Organisation set up the three-step analgesic ladder in order to better clarify the optimal pharmacological approach in order to achieve a good balance between pain control and adverse related effects. The objective of this study is to analyse the changes observed in the use of the WHO analgesic ladder drugs in relation of pain intensity in a population of advanced cancer patients attended in the out-patient clinic (OPC).The study was carried out on a consecutive sample of advanced cancer patients attended at the OPC. Inclusion criteria: age >18 years, diagnosis of advanced cancer, lack of cognitive impairment (Pfeiffer test ≤ 4), pain with VAS > 3 on first evaluation and agreed to participate. Variables recorded: Categorical variables were summarized as percentages (absolute numbers). The sample was divided according to pain intensity on the first evaluation (VAS < 7 vs ≥7) and the analgesic regime used according to the WHO analgesic ladder (first/second/third step). The third step was further divided in long acting opioid (LAO), short acting opioids (SAO) and rapid onset opioids (ROO).We used the chi-squared test to compare groups. For the significative differences (P < 0,05) the McNemar test was applied. A total of 211 patients were included in the study. Mean of age 64, 0 ± 14 years. Men 87, 2%. Lung cancer 41, 2%; Upper-digestive 15, 6%. 136 patients with an initial VAS ≥ 7 (64,45%). Differences were found in the second step of the WHO on pain control (P = .045). Regarding the third step, the differences were related to the first evaluation: third step (global) P = .002, LAO (P = .028) and ROO (P = .043). Those data suggest that significative differences can be found between the use of the different analgesics the WHO ladder and pain intensity.

Incidence and factors contributing to postdischarge nausea and vomiting in pediatric ambulatory surgical cases.

Little is known regarding the incidence and contributing factors of postdischarge nausea and vomiting in children. The aim of this study was to determine the incidence of postdischarge nausea and vomiting in day surgery patients and to identify demographic, intraoperative, and postoperative variables that influence the risk. In this prospective observational study, a postdischarge questionnaire was administered to parents of ambulatory patients who received anesthesia and the electronic records were reviewed. Of 1041 ambulatory patients who received general anesthesia, 143 (14%) experienced postdischarge nausea and vomiting. Patients who did not receive intraoperative opioids had a lower incidence (8%) than those who received short-acting opioids (14%) (difference of 6%, 95% CI 1.9%-10.2%, P<.001) or long-acting opioids (24%) (difference of 16%, 95% CI 8.1%-24.3%, P<.001). Patients who received short-acting opioids also had a lower incidence than those who received long-acting opioids (difference of 10%, 95% CI 2.2%-18.1%, P<.001). The incidence also differed between those patients who received postdischarge opioids at home (29%) and those who did not (13%) (difference of 16%, 95% CI 7.5%-27.6%, P<.001). There was no association with age, gender, airway management, nitrous oxide use, amount of intravenous fluids, duration of anesthesia, intraoperative antiemetic administration or dosage, length of time from recovery room discharge to first oral intake, or length of ride home from the hospital. Multivariate generalized linear regression analysis confirmed intraoperative (short-acting opioids odds ratio 1.686, 95% CI 1.020-2.787; long-acting opioids odds ratio 3.093, 95% CI 1.634-5.874) and postdischarge (odds ratio 2.037 95% CI 1.142-3.632) opioids to be independent risk factors for postdischarge nausea and vomiting. We found an incidence of postdischarge nausea and vomiting of 14%. Intraoperative and postdischarge opioids increase the risk, with long-acting intraoperative opioids further accentuating the risk.

Primary care physician opinion survey on FDA Opioid Risk Evaluation and Mitigation Strategies

In response to disturbing rises in prescription opioid abuse, the Food and Drug Administration (FDA) has proposed the implementation of aggressive Risk Evaluation and Mitigation Strategies (REMS) that will require prescribers to obtain mandatory education, provide mandatory patient education, register patients into registries, and so forth before prescribing certain opioids. The first opioid to be subject to the new REMS was the recently approved fentanyl buccal soluble film (Onsolis). The FDA plans to extend mandatory REMS to other opioids, including all rapid-onset formulations and eventually all long-acting opioids, whether or not they already have FDA approval. To assess the likely impact of REMS on opioid prescribing, the authors conducted a survey of how REMS implementation might affect opioid prescribing. After obtaining Institutional Review Board's approval, a survey regarding opioid prescribing was sent via e-mail to 2,800 physician members of the Pennsylvania Academy of Family Physicians. Practicing family practice physicians were asked to respond to questions regarding their current opioid prescribing, and how various components of REMS might alter their future opioid prescribing. A total of 259 surveys were completed. Of the 259 physicians who responded, 87 percent reported themselves as being primary care practitioners; others identified themselves as specialists. Of all respondents, 96 percent currently prescribe opioids for acute pain, 77 percent for cancer pain, and 83 percent for chronic nonmalignant pain. The respondents were split from 52 percent to 48 percent in terms of being in an urban versus a rural practice setting. Forty eight percent of all respondents reported their willingness to complete no more than 2 hours of training if it were available locally to be able to continue prescribing opioids. A similar percentage (50 percent) also said that they would encourage patient compliance with education and register their patients on a 6-month basis. However, the following percent of respondents reported that they would discontinue prescribing an opioid product if required to comply with the following REMS requirement: obtain 4-8 hours of straining, followed by 2 hours of pain-related continuing medical education every 2 years (13.4 percent); complete mandatory patient education (12.2 percent); document ongoing monitoring of therapy including efficacy, safety, and monitoring for aberrant drug-related behavior (10.4 percent); or register each patient in a patient registry, and have the patient re-registered every 6 months (18.3 percent). The results suggest that 50 percent of the responding physicians would be willing to comply with the mandatory education component of REMS, including the requirement to provide education to patients. For some REMS components, willingness to continue to prescribe despite the restriction was higher (up to 90 percent). However, this leaves a substantial proportion of physicians who would not be willing to prescribe opioids controlled by the new REMS, which could have the unintended effect of decreasing access to these medications for legitimate medical purposes.

Dose and Duration of Opioid Use in Propensity Score–Matched, Privately Insured Opioid Users With and Without Spinal Cord Injury

ObjectivesTo (1) compare the opioid utilization patterns in opioid users with spinal cord injury (SCI) to a propensity score–matched general population of opioid users without SCI; and (2) identify characteristics of persons with SCI associated with long-term and/or high-dose use of opioids. DesignQuasi-experimental analysis of archival data. SettingData used for the analysis were derived from Thompson Reuters MarketScan Commercial Claims and Encounters Databases for the years 2012 to 2013. ParticipantsParticipants (N=2908; aged 18–64y) included opioid users with SCI (n=1454) and propensity score–matched opioid users without SCI (n=1454). The cohorts were matched using demographics including comorbidities, hospital admissions, age, sex, and geographic region. InterventionsNot applicable. Main Outcome MeasuresMedical and pharmacy claims from 2012 to 2013 MarketScan data were analyzed to characterize whether persons were short-term (<90d) or long-term (≥90d) opioid users, and whether persons had high (≥120mg) or low (<120mg) average daily morphine equivalents. ResultsPersons with SCI were significantly more likely to be long-term users of low-dose, short-acting opioids (P<.0001) and more likely to be taking high morphine-equivalent doses of long-acting opioids (P<.0001) than matched controls. Among persons with SCI, those with lumbar/sacral injuries had more days' supply of high-dose, long-acting opioids than did persons with thoracic or cervical injuries. ConclusionsPersons with SCI are prescribed opioids for longer durations and at higher morphine-equivalent doses than controls, which may increase the risk of opioid dependence or adverse drug events. Findings should be considered in the development of practice guidelines for alternate pain management options or opioid dependence interventions for persons with SCI.

141: Long acting opioid use during delivery hospitalizations and risk for severe maternal morbidity

Currently, there is limited data on long acting opioid (LAO) use during delivery hospitalizations including whether women using these medications are at increased risk for severe maternal morbidity (SMM). The objectives of this study were: (i) to assess use of and hospital variation in LAOs during delivery hospitalizations, and (ii) determine risk for SMM among LAO users. An administrative inpatient database that includes medications was analyzed to evaluate use of LAOs during delivery hospitalizations from January 2006 through March 2015. Medications included extended-release formulations of oxycodone and morphine, buprenorphine, and methadone. Hospital level rates of LAO administration during delivery hospitalizations were calculated. Unadjusted and adjusted models evaluating the role of demographic and hospital factors were created. Risk for SMM was determined based on CDC criteria. 4,653,945 delivery hospitalizations meeting criteria were included in the analysis. 1.2% of women received a LAO during their hospitalization. Risk of SMM was significantly higher for women receiving a LAO compared to other women (3.0% vs. 1.6% p<0.001). The Figure demonstrates rates of LAO use by hospital. Of 497 hospitals, rate of LAO receipt was ≤0.1% for 158 hospitals, >0.1% and <1.0% for 254 hospitals, and ≥1.0% for 85 hospitals; this latter group accounted for majority of LAO use. In adjusted analyses, LAO use was more common among older women, white women, Medicaid recipients, and single women (Table). LAO use varies significantly by center and is associated with an increased risk for SMM. Given that a small proportion of centers provide care for the majority of women using these medications, it may be possible to improve care and safety via targeted interventions.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Intravenous dexamethasone for prophylaxis of postoperative nausea and vomiting after administration of long-acting neuraxial opioids: a systematic review and meta-analysis.

Long-acting neuraxial opioids provide excellent analgesia after surgery, but are associated with higher rates of postoperative nausea and vomiting. Dexamethasone effectively prevents postoperative nausea and vomiting after general anaesthesia, but its value in patients receiving long-acting neuraxial opioids is undetermined. Therefore, the objective of this meta-analysis was to assess the prophylactic anti-emetic efficacy of intravenous (i.v.) dexamethasone in this population. The study methodology followed the PRISMA statement guidelines. The primary outcome was the need for rescue anti-emetics during the first 24 postoperative hours, analysed according to the dose of dexamethasone (low-dose 2.5-5.0 mg; intermediate dose 6.0-10.0 mg), timing of administration (beginning or end of surgery) and route of long-acting opioid administration (intrathecal or epidural). Additionally, the rates of complications (restlessness, infection, hyperglycaemia) were sought. Thirteen trials were identified, representing a total of 1111 patients. When compared with placebo, intravenous dexamethasone reduced the need for rescue anti-emetics (risk ratio (95%CI) 0.44 (0.35-0.56); I2 = 43%; p < 0.00001; quality of GRADE evidence: moderate), without differences between dexamethasone doses (p for sub-group difference = 0.67), timing of administration (p for sub-group difference = 0.32) or route of long-acting opioid (p for sub-group difference = 0.10). No patients developed infection or restlessness among trials that sought these complications. No trial measured blood glucose levels. In conclusion, there is enough evidence to state that intravenous dexamethasone provides effective anti-emetic prophylaxis during the first 24 postoperative hours in patients who receive long-acting neuraxial opioids.

Pain and Opioid Use after Reversal of Sickle Cell Disease Following Hematopoietic Stem Cell Transplant

Introduction: Pain is the most common symptom of sickle cell disease (SCD). Hematopoietic stem cell transplant (HSCT) is currently the only curative therapy for SCD; however, some patients continue to report pain requiring opioid treatment despite hematologic cure following successful HSCT. Knowledge of factors associated with continued pain and opioid use may help reduce post-HSCT pain-related morbidity. We analyzed data from a cohort of SCD patients who have been successfully treated by nonmyeloablative HLA-matched sibling allogeneic HSCT. Our goal was to investigate pre-HSCT factors that are associated with continued pain and opioid use at 12 months after a successful HSCT.Methods: Detailed data on the clinical course, pain, opioid use, and laboratory values were collected from medical records at 3 months pre-HSCT and 12 months post-HSCT (n=35). Patient Reported Outcomes Measurement Information System (PROMIS) measures were available in a subgroup of these patients (n=20), also collected at the same time points. Patients with pre-HSCT pain were classified using Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks-American Pain Society Pain Taxonomy (AAPT) guidelines into one of three pain categories: 1. Chronic pain without contributory SCD complication; 2. Chronic pain explained by contributory SCD complication, eg. avascular necrosis; 3. Chronic pain with a mixed pain phenotype (eg. some pain explained by a contributory SCD complication but also pain occurring in unrelated sites). Patients who only experienced acute episodic pain were grouped separately (Episodic pain only).Results: The median age of the cohort was 30.5 years (range: 16-65 years) and 21 (60%) patients were male. Pre-HSCT, all patients experienced intermittent episodes of pain. Forty-six% of the patients experienced acute episodic pain only, 26% also had chronic pain with a contributory SCD complication and 28% also had chronic pain without contributory SCD complication or a mixed pain phenotype. Post-HSCT, median pain-related admissions decreased significantly (from 3 admissions/year (range 0-24) pre-HSCT to 0 (range 0-3) post-HSCT; (p<0.001)). There were significant reductions in the prescription of both short- and long-acting opioids pre- vs post-HSCT (91% to 40% for short acting and 40% to 14% for long acting opioids; p<0.001). While 14 out of 35 (40%) reported pain at 12 months post-HSCT, examination of continued opioid use patterns across the AAPT groups showed that in the group of chronic pain patients without contributory SCD complications, 90% continued to use opioids to manage their pain whereas none of the patients in the episodic pain only group received opioids post-HSCT and for the group of patients with chronic pain related to a SCD complication, 50% stopped using opioids post-transplant.Analysis of PROMIS data, showed significant improvement in the subscales of Pain Intensity (p=0.03), Pain Impact (p=0.007), Satisfaction with Social Role (p= 0.03), and Physical Function (p= 0.004) following HSCT but no significant changes were seen for Fatigue (p=0.09), Anxiety, Depression or Sleep Disturbance (which may be explained by the small sample size not having enough variance). However, when comparing patients with persistent pain and opioid use without related SCD complications (n=6) versus those with resolved pain post-HSCT (n=9), pre-HSCT Anxiety ratings were significantly higher in the group with unexplainable, persistent pain (p=0.05). For those same groups, additional pre-HSCT factors that were associated with unexplainable, persistent pain post-HSCT were higher burden of pain as defined by higher median pain admissions/year (2 (0-10) vs. 5.5 (3-9); p=0.04); higher overall numerical pain rating on a 0-10 scale (2 (0-5) vs. 6 (5-7); p=0.02) and treatment with long acting opioids (0% vs. 86%; p<0.001).Conclusions: SCD patients with higher pre-HSCT pain burden (more pain admissions and higher pain intensity ratings), long-acting opioid use and certain psychological traits (anxious disposition) may be at risk for persistent pain and continued opioid use post-HSCT. Future studies should evaluate outcomes beyond 12 months of follow up, further characterize underlying mechanisms and evaluate potential interventions to reduce pain and opioid use related morbidities in this subset of patients. DisclosuresNo relevant conflicts of interest to declare.

Changes in the dispensing of opioid medications in Canada following the introduction of a tamper-deterrent formulation of long-acting oxycodone: a time series analysis.

In February 2012, a reformulated tamper-deterrent form of long-acting oxycodone, OxyNeo, was introduced in Canada. We investigated the impact of the introduction of OxyNeo on patterns of opioid prescribing. We conducted population-based, cross-sectional analyses of opioid dispensing in Canada between 2008 and 2016. We estimated monthly community pharmacy dispensing of oral formulations of codeine, morphine, hydromorphone and oxycodone, and a transdermal formulation of fentanyl, and converted quantities to milligrams of morphine equivalents (MMEs) per 1000 population. We used time series analysis to evaluate the effect of the introduction of OxyNeo on these trends. National dispensing of long-acting opioids fell by 14.9% between February 2012 and April 2016, from 36 098 MMEs to 30 716 MMEs per 1000 population (p < 0.01). This effect varied across Canada and was largest in Ontario (reduction of 22.8%) (p = 0.01) and British Columbia (reduction of 30.0%) (p = 0.01). The national rate of oxycodone dispensing fell by 46.4% after the introduction of OxyNeo (p < 0.001); this was partially offset by an increase of 47.8% in hydromorphone dispensing (p < 0.001). Although dispensing of immediate-release opioids was a substantial contributor to overall population opioid exposure across Canada, it was unaffected by the introduction of OxyNeo (p > 0.05 in all provinces). The findings suggest that the introduction of a tamper-deterrent formulation of long-acting oxycodone in Canada, against a background of changing public drug benefits, was associated with sustained changes in selection of long-acting opioids but only small changes in the quantity of long-acting opioids dispensed. This illustrates the limited effect a tamper-deterrent formulation and associated coverage policy can have when other, non-tamper-deterrent alternatives are readily available.

Short-Acting Opioids Are Associated with Comparable Analgesia to Long-Acting Opioids in Patients with Chronic Osteoarthritis with a Reduced Opioid Equivalence Dosing.

There are no studies that exist within the primary care setting that address optimal opioid therapy in osteoarthritis patients. In light of the recently released US Centers for Disease Control and Prevention guidelines on opioid use in chronic noncancer pain, there is a pressing need to better characterize the effectiveness of long- and short-acting opioids. To examine the effectiveness of short-acting opioids (SAO) vs long-acting opioids (LAO) and combination therapies (SAO and LAO) for treating chronic osteoarthritis pain in a retrospective trial. Average and lowest pain scores approximately one to two weeks prior to patient appointments were collected and averaged for both SAO and LAO patients who were actively enrolled in a pain clinic at an academic medical center. There was no statistical difference between reported average and low pain scores for the SAO vs LAO groups (P = 0.201 and P = 0.296, respectively), although the SAO group on average had a significantly lower morphine equivalence (P < 0.001). Various covariates for both groups were tested in an adjusted model to look at trends in the use of nonopioid medications (i.e., acetaminophen, nonsteroidal anti-inflammatory drugs, antidepressants, and adjunct analgesic agents). No significant differences in pain scores existed when comparing covariates for the SAO vs LAO groups. The study suggests that in addition to being effective, short-acting opioid medications may also provide a safer and cheaper alternative to long-acting opioid therapies in the treatment of chronic osteoarthritis. This article investigates the effectiveness of short-acting vs long-acting opioids for the treatment of chronic noncancer pain, specifically osteoarthritis. This information could potentially aid practitioners in primary care environments to design equally efficacious and less costly opioid regimens, while simultaneously enhancing patient safety.