Deprescribing Opioids in Chronic Non-cancer Pain: Systematic Review of Randomised Trials.

BACKGROUND: Deprescribing, the process of reducing or discontinuing unnecessary or harmful medicines is an essential part of clinical practice. OBJECTIVE: To evaluate the efficacy of interventions designed to deprescribe opioid analgesics for pain relief in patients with chronic non-cancer pain. METHODS: We searched electronic databases, including clinical trial registries, from database inception to 13th January 2020 without restrictions, and conducted citation tracking. Our systematic review included randomised controlled trials (RCTs) evaluating interventions reducing the prescription, or use of opioid analgesics in patients with chronic pain versus control. Inventions could be aimed at the patient, clinician, or both. We excluded trials enrolling patients with cancer or illicit drug use. Two authors independently screened and extracted data. Outcome follow-up timepoints were short (≤ 3 months), intermediate (> 3 but < 12 months) or long (≥ 12 months) term. Primary outcome was the reduction in opioid dose [morphine milligram equivalent (MME) mg/day]. Methodological quality was assessed using the Cochrane Risk of Bias Tool. RESULTS: We included ten patient-focused RCT interventions (n = 835; median 37 participants) and 2 testing clinician-focused interventions (n = 291 clinicians); none at low risk of bias. Patient-focused interventions did not reduce opioid dose in the intermediate term [e.g. dose reduction protocol, mean difference (MD) - 19.9 MME, 95% CI - 107.5 to 67.7], nor did they increase the number of participants who ceased their dose, or increase the risk of serious adverse events or adverse events. One clinician intervention of education plus decision tools versus decision tools alone reduced the number of opioid prescriptions (risk difference (RD) - 0.1, 95% CI - 0.2 to - 0.1), dose (MD - 5.3 MME, 95% CI - 6.2 to - 4.5) and use (RD - 0.1, 95% CI - 0.1 to - 0.0) in the long term. LIMITATIONS: Study heterogeneity prevented meta-analysis. CONCLUSION: The small number of studies and heterogeneity prevented firm conclusions to recommend any one opioid-analgesic-deprescribing strategy in patients with chronic pain. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42017068422.

Drivers of the opioid crisis: An appraisal of financial conflicts of interest in clinical practice guideline panels at the peak of opioid prescribing.

BACKGROUND: Starting in the late 1990s, the pharmaceutical industry sought to increase prescribing of opioids for chronic non-cancer pain. Influencing the content of clinical practice guidelines may have been one strategy industry employed. In this study we assessed potential risk of bias from financial conflicts of interest with the pharmaceutical industry in guidelines for opioid prescribing for chronic non-cancer pain published between 2007 and 2013, the peak of opioid prescribing. METHODS: We used the Guideline Panel Review (GPR) to appraise the guidelines included in the 2014 systematic review and critical appraisal by Nuckols et al. These were English language opioid prescribing guidelines for adults with chronic non-cancer pain published between July 2007 and July 2013, the peak of opioid prescribing. The GPR assigns red flags to items known to introduce potential bias from financial conflicts of interest. We operationalized the GPR by creating specific definitions for each red flag. Two reviewers independently evaluated each guideline. Disagreements were resolved with discussion. We also compared our score to the critical appraisal scores for overall quality from the study by Nuckols et al. RESULTS: We appraised 13 guidelines, which received 43 red flags in total. Guidelines had 3.3 red flags on average (out of a possible seven) with range from one to six. Four guidelines had missing information, so red flags may be higher than reported. The guidelines with the highest and second highest scores for overall quality in the 2014 critical appraisal by Nuckols et al. had five and three red flags, respectively. CONCLUSION: Our findings reveal that the guidelines for opioid prescribing chronic non-cancer pain from 2007 to 2013 were at risk of bias because of pervasive conflicts of interest with the pharmaceutical industry and a paucity of mechanisms to address bias. Even highly-rated guidelines examined in a 2014 systematic review and critical appraisal had many red flags.

Optimizing Opioid-Prescribing Practices After Parathyroidectomy.

BACKGROUND: To help control opioid overprescription, we conducted a large institutional, 3-site initiative to provide discharge prescribing guidelines for different procedures. Our aim is to refine institutional guidelines for parathyroidectomy. METHODS: Patients undergoing parathyroidectomy completed a 28-question survey about opioid consumption. Discharge opioid prescription amounts were converted into morphine milligram equivalents (MMEs) and reported as median and interquartile range (IQR). Consumption was dichotomized into top quartile MME users (Q4) versus standard users (Q1, Q3). Univariate analysis compared opioid consumption. RESULTS: A total of 91 patients were included; 90% were opioid-naive. While the median prescribed was 75 (IQR 75, 150) MME, the median consumed was 0 (IQR 0, 20). Top users reported higher pain scores [median (IQR): 2 (2, 4)] compared to standard users [1 (0, 3), P = 0.01]. However, there was no difference in opioid consumption between unilateral neck exploration, bilateral exploration, or thyroidectomy and parathyroidectomy, P = 0.11. There was no difference in opioid consumption by age, sex, or BMI (all P > 0.05). Of those receiving a prescription, 94.6% had left-over opioids at the time of survey, resulting in 82% of prescribed opioids being unused. CONCLUSIONS: Over half of patients undergoing parathyroidectomy did not consume any opioid, and very few needed more than 2 d of opioid. Moreover, most patients did not dispose the unused opioids, which put these pills at risk of diversion and misuse. Surgical approach did not change consumption, illustrating that these guidelines are applicable to thyroidectomy given the similarity between techniques. We recommend prescribing nonopioid analgesics for patients undergoing parathyroidectomy.

Comparing Nonopioids Versus Opioids for Acute Pain in the Emergency Department: A Literature Review.

BACKGROUND: Pain is the most common reason for patient visits in the emergency department (ED). Opioids have been long considered the standard of care for acute pain in the ED. Because of the opioid crisis, investigation and implementation of novel practices to manage pain is needed. The use of various nonopioids has been suggested as a plausible alternative to opioids, with emerging literature to support its use for acute pain in the ED. STUDY QUESTION: To evaluate the safety, efficacy, opioid-sparing effects of nonopioids in patients who present with acute pain in the ED. DATA SOURCES: We systematically searched PubMed and EMBASE (July 1970 to January 2019). STUDY DESIGN: Randomized controlled trials that evaluated nonopioids versus opioids in the ED were eligible. The clinical outcomes measured were change in pain scores compared with baseline, the incidence of adverse events, and use of rescue analgesia. RESULTS: Twenty-five randomized controlled trials that evaluated the use of nonopioids in 2323 patients [acetaminophen (APAP) (n = 651), diclofenac (n = 547), ketamine (n = 272), ketorolac (n = 225), lidocaine (n = 219), ibuprofen (n = 162), ibuprofen & APAP (n = 162), hydroxyzine & dihydroergotamine (n = 85)] met inclusion criteria. Four trials found significant greater reductions in pain scores, favoring nonopioids. In all trials, the duration of pain relief provided by nonopioids was not sustained over an extended period. Eighteen trials reported no significant differences in reduction of pain scores. Two trials reported improved pain reduction with opioids and one trial reported noninferiority. CONCLUSIONS: Evidence from primary literature suggests that nonopioids could be a feasible alternative to opioids for management of acute pain in the ED as it is effective, safe, and decreases the need for rescue analgesia.

The opioid crisis: Origins, trends, policies, and the roles of pharmacists.

PURPOSE: The purpose of this review is to (1) provide information concerning the opioid crisis including origins, trends, and some important related laws/policies; and (2) summarize the current involvement and impact of pharmacists in helping to address the crisis, as well as examine practices in other healthcare disciplines from which pharmacists might derive guidance and strategies. SUMMARY: Contributors to the opioid crisis included campaigns to treat pain as a fifth vital sign and to use opioids in treatment of non-cancer-related pain, as well as aggressive marketing of opioid analgesics by pharmaceutical companies. To address the crisis, numerous strategies have been implemented at the policy/legislative, health-system, and patient levels, such as prescription drug monitoring programs (PDMPs), increased regulation of pain clinics, and expanded use of naloxone. Pharmacists have a critical role to play in interventions to address opioid misuse and reduce harm resulting from misuse. Such interventions include patient screening and risk stratification, patient and community education and outreach concerning appropriate pain management, medication reviews/medication therapy management, education on safe storage and disposal, distribution of naloxone/opioid rescue kits and training on their proper use, and referral of patients to addiction treatment, among other strategies. CONCLUSION: Pharmacists have multiple, complex roles in addressing the opioid crisis. Outcomes of several studies provide substantial evidence that pharmacists can make an impact through appropriate pain management, use of PDMPs, opioid overdose prevention training, and medication reviews and counseling, among other interventions.

Regional anesthesia for cardiac surgery.

PURPOSE OF REVIEW: Anesthesia for cardiac surgery has traditionally utilized high-dose opioids to blunt the sympathetic response to surgery. However, recent data suggest that opioids prolong postoperative intubation, leading to increased morbidity. Given the increased risk of opioid dependency after in-hospital exposure to opioids, coupled with an increase in morbidity, regional techniques offer an adjunct for perioperative analgesia. The aim of this review is to describe conventional and emerging regional techniques for cardiac surgery. RECENT FINDINGS: Well-studied techniques such as thoracic epidurals and paravertebral blocks are relatively low risk despite lack of widespread adoption. Benefits include reduced opioid exposure after paravertebral blocks and reduced risk of perioperative myocardial infarction after epidurals. To further lower the risk of epidural hematoma and pneumothorax, new regional techniques have been studied, including parasternal, pectoral, and erector spinae plane blocks. Because these are superficial compared with paravertebral and epidural blocks, they may have even lower risks of hematoma formation, whereas patients are anticoagulated on cardiopulmonary bypass. Efficacy data have been promising, although large and generalizable studies are lacking. SUMMARY: New regional techniques for cardiac surgery may be potent perioperative analgesic adjuncts, but well-designed studies are needed to quantify the effectiveness and safety of these blocks.

Inconsistency in Opioid Prescribing Practices After Pediatric Ambulatory Hernia Surgery.

INTRODUCTION: Nonmedical opioid use is a major public health problem. There is little standardization in opioid-prescribing practices for pediatric ambulatory surgery, which can result in patients being prescribed large quantities of opioids. We have evaluated the variability in postoperative pain medication given to pediatric patients following routine ambulatory pediatric surgical procedures. METHODS: Following IRB approval, pediatric patients undergoing umbilical hernia repair, inguinal hernia repair, hydrocelectomy, and orchiopexy from 2/1/2017 to 2/1/2018 at our tertiary care children's hospital were retrospectively reviewed. Data collected include operation, surgeon, resident or fellow involvement, utilization of preoperative analgesia, opioid prescription on discharge, and patient follow-up. RESULTS: Of 329 patients identified, opioids were prescribed on discharge to 37.4% of patients (66.3% of umbilical hernia repairs, 20.6% of laparoscopic inguinal hernia repairs, and 33.3% of open inguinal hernia repairs [including hydrocelectomies and orchiopexies]). For each procedure, there was large intrasurgeon and intersurgeon variability in the number of opioid doses prescribed. Opioid prescription ranged from 0 to 33 doses for umbilical hernia repairs, 0 to 24 doses for laparoscopic inguinal repairs, and 0 to 20 doses prescribed for open inguinal repairs, hydrocelectomies, and orchiopexies. Pediatric surgical fellows were less likely to discharge a patient with an opioid prescription than surgical resident prescribers (P < 0.01). In addition, surgical residents were more likely to prescribe more than twelve doses of opioids than pediatric surgical fellows (P < 0.01). Increasing patient age was associated with an increased likelihood of opioid prescription (P < 0.01). There were two phone calls and two clinic visits for pain control issues with equal numbers for those with and without opioid prescriptions. CONCLUSIONS: There is significant variation in opioid-prescribing practices after pediatric surgical procedures; increased awareness may help minimize this variability and reduce overprescribing. Training level has an impact on the frequency and quantity of opioids prescribed.

Methodologic limitations of prescription opioid safety research and recommendations for improving the evidence base.

PURPOSE: The ongoing opioid epidemic has claimed more than a quarter million Americans' lives over the past 15 years. The epidemic began with an escalation of prescription opioid deaths and has now evolved to include secondary waves of illicit heroin and fentanyl deaths, while the deaths due to prescription opioid overdoses are still increasing. In response, the Centers for Disease Control and Prevention (CDC) moved to limit opioid prescribing with the release of opioid prescribing guidelines for chronic noncancer pain in March 2016. The guidelines represent a logical and timely federal response to this growing crisis. However, CDC acknowledged that the evidence base linking opioid prescribing to opioid use disorders and overdose was grades 3 and 4. METHODS: Motivated by the need to strengthen the evidence base, this review details limitations of the opioid safety studies cited in the CDC guidelines with a focus on methodological limitations related to internal and external validity. RESULTS: Internal validity concerns were related to poor confounding control, variable misclassification, selection bias, competing risks, and potential competing interventions. External validity concerns arose from the use of limited source populations, historical data (in a fast-changing epidemic), and issues with handling of cancer and acute pain patients' data. We provide a nonexhaustive list of 7 recommendations to address these limitations in future opioid safety studies. CONCLUSION: Strengthening the opioid safety evidence base will aid any future revisions of the CDC guidelines and enhance their prevention impact.

Clinical solutions to chronic pain and the opiate epidemic.

The current opiate epidemic has caused tens of thousands of deaths annually and hundreds of billions in economic losses. From 1979 to 2015, accidental opiate-related deaths increased by 4250%. Despite its magnitude, the driving forces remain poorly understood. A narrow understanding by physicians, administrators and policy makers has resulted in a clinical approach to chronic pain treatment misguided by expediency, shortsighted cost reduction, pharmaceutical profit, and patient satisfaction. Until the broken elements are well understood, effective policy solutions will remain elusive. In this review, we describe the first comprehensive timeline of significant contributing factors between 1979 and the present. To address the complexity of treating patients with chronic pain and its contribution to opiate overuse, we outline an alternative clinical and health systems approach to chronic pain therapy. Addressing the underlying drivers will require empowering physicians to use clinical judgment over guidelines and algorithms to provide holistic, high-quality healthcare to individual victims of the opiate epidemic.

Understanding multi-pill ingestion of prescription opioids: Prevalence, characteristics, and motivation.

PURPOSE: Oral use is the primary route of administration among non-medical prescription opioid users. While progression to non-oral routes and shifts to stronger opioids have been previously studied as ways to cope with tolerance, the prevalence and patterns of those who cope by increasing the number of pills/tablets ingested at one time (ie, multi-pill use) has not been assessed. METHODS: A subset (N = 231) of treatment-seeking opioid users from a national opioid surveillance system, participating in the Researchers and Participants Interacting Directly (RAPID) Program, completed an online survey centered on multi-pill use. RESULTS: Over two-thirds of non-medical prescription opioid users had a history of multi-pill use (67.7%), defined as ingesting four or more of the same pill, intact and at the same time. Among these (n = 154), the median maximum number of pills taken at one time was eight, with over 20% ingesting 11 or more pills in a single instance. Nearly half engaged in multi-pill ingestion more than once a day in the past month (43.8%), with accessibility to lower dose pills being the primary motivator (85.4%). Hydrocodone immediate-release (IR) compounds were by far the most frequently endorsed (90.3%), followed by oxycodone IR tablets with acetaminophen (76.0%) and oxycodone IR tablets containing no acetaminophen/ibuprofen (56.5%). CONCLUSIONS: These results indicate that the ingestion of multiple opioid pills/tablets is extremely common among treatment-seeking opioid users. This, and other forms of non-medical oral use of prescription opioids, should be taken under consideration when developing prevention and intervention efforts targeting the opioid epidemic.