High-potency Opioids Research Articles

The "Micro"cosm: Magnifying the Nuance of Low Dose Buprenorphine Inductions.

Now that the X-wavier is a thing of the past, patients with Opioid Use Disorder (OUD) who previously lacked access to buprenorphine may have access to lower barrier care and may be looking to make the transition from either methadone or illicit fentanyl to buprenorphine. This can be quite challenging and both fentanyl and methadone are hihghly potent drugs and can result in a difficult transtition to buprenorphine. A transition from high potency opioids to buprenorphine is challenging and can cause discomfort or withdrawal in patients. Procedures/data/observations: Patients tend to have a difficult time when undergoing a transition from significant fentanyl use (> 1 bundle/day) or high dose methadone to buprenorphine. Over the last year, we've supported this transition for our hospitalized patients and have learned some tips and tricks to ease the transitions. Through our work we've come up with a strategy to transition patients that includes utilizing full mu agonists while initiating a low dose buprenorphine induction. We have developed an informal protocol for this transition that takes advantage of the flexibility of low dose buprenorphine induction strategies and includes the use of non-opioid adjuvant medications to control symptoms of discomfort and withdrawal. A transition from the use of significant fentanyl or high dose methadone to buprenorphine is possible and can take place over a matter of a few days. Such a transition requires careful attention to patient symptoms, availability of as needed short acting opioids, and the judicious use of non-opioid adjuvants.

Pain Management in Patients with Hepatorenal Syndrome: A Literature Review

Introduction: Patients with cirrhosis often present with pain as a common complaint. Pharmacological pain management safety depends on the excretion and metabolism of drugs by the kidney and the liver. The analgesic choice in cirrhotic patients can be tremendously challenging, especially in patients with hepatorenal syndrome, a potentially reversible renal impairment associated with an increased drug accumulation and a high risk of potential toxicity. Choice and dose of medications depend on various factors, including the severity of the condition, possible drug interactions, drug dependence, and liver transplant status. Ideally, medications should be titrated from the lowest effective dose to higher strength. This review aims to discuss the pharmacodynamic and pharmacokinetics of analgesics used in cirrhotic patients. The metabolism of each drug, route of administration, pathophysiology, and limitations of their use are discussed to better understand their implementation in patients with cirrhosis and HRS. For this purpose, we performed a systematic literature search in PubMed and Google Scholar. Articles were searched via search terms and keywords. Certain high potency opioids like Sufentanil, Fentanyl, Remifentanil, Oxymorphone, and Butorphanol can be used cautiously. Low potency opioids such as Pentazocine, Tramadol, Nalbuphine, and Tapentadol may also be considered with dose adjustments. Albeit less favorable, some other analgesic options include Gabapentin, Pregabalin, acetaminophen, Duloxetine, Venlafaxine, Fluoxetine, Topical Lidocaine, Capsaicin, and Clonidine. Methodology: A systematic literature search in PubMed and google scholar was conducted between March 5 and August 10, 2021. Articles were searched via search terms and keywords relating to International Classification of Diseases: hepatorenal syndrome, pain, opioids, metabolism, renal clearance. Results: One thousand three hundred eighty-seven articles were identified from database searching. After removal of duplicates, 924 studies were screened for eligibility. After review of titles and abstracts, 665 studies were rejected for relevance reasons. Most of these studies were rejected because they were not relevant, did not meet search criteria, case-control article, case series articles, no English translation, articles did not mention adjustments in patients with liver or kidney disease. One hundred forty-two articles were used for the synthesis.

Treating Adolescents With Opioid Use Disorder: A Medication-Assisted Treatment Approach

With drug-related overdose death involving opioids hitting record numbers in 2021, clinical mental health counselors (CMHCs) need to be prepared to address the needs of adolescent clients with opioid use disorder (OUD). Adolescent populations with OUD have significant risk factors and poor outcomes and are at elevated risk for an opioid-related overdose due to surges in high-potency opioids. Medication-assisted treatment (MAT) has been an evidenced-based treatment option for adolescents that combines pharmacotherapy and behavioral therapies to treat OUD. This article reviews the adolescent MAT literature and provides clinical implications for CMHCs working with adolescent populations diagnosed with OUD. The medications and behavioral therapies utilized in MAT are highlighted in this article, and a case study provides additional context.

Do patients addicted to fentanyl need higher doses of methadone or buprenorphine?

With most medical conditions, such as high blood pressure, there are many choices of medications. For opioid use disorder (OUD), there are three: methadone, buprenoprhine, and naltrexone, and because of issues with naltrexone—patients don't want it, induction requires a week opioid‐free first—that leaves methadone and buprenorphine. The question in the illicit fentanyl era is: Which medication works best for patients addicted to high levels of high potency opioids like fentanyl? ADAW asked top experts in the field and found out that there is no cookie‐cutter recipe; that people with OUD, just like people with high blood pressure, need individualized care. On top of that, many people with OUD have severe other problems and need comprehensive care, regardless of what medication is chosen.

Treatment of opioid overdose: current approaches and recent advances.

BackgroundThe USA has recently entered the third decade of the opioid epidemic. Opioid overdose deaths reached a new record of over 74,000 in a 12-month period ending April 2021. Naloxone is the primary opioid overdose reversal agent, but concern has been raised that naloxone is not efficacious against the pervasive illicit high potency opioids (i.e., fentanyl and fentanyl analogs).MethodsThis narrative review provides a brief overview of naloxone, including its history and pharmacology, and the evidence regarding naloxone efficacy against fentanyl and fentanyl analogs. We also highlight current advances in overdose treatments and technologies that have been tested in humans.Results and conclusionsThe argument that naloxone is not efficacious against fentanyl and fentanyl analogs rests on case studies, retrospective analyses of community outbreaks, pharmacokinetics, and pharmacodynamics. No well-controlled studies have been conducted to test this argument, and the current literature provides limited evidence to suggest that naloxone is ineffective against fentanyl or fentanyl analog overdose. Rather a central concern for treating fentanyl/fentanyl analog overdose is the rapidity of overdose onset and the narrow window for treatment. It is also difficult to determine if other non-opioid substances are contributing to a drug overdose, for which naloxone is not an effective treatment. Alternative pharmacological approaches that are currently being studied in humans include other opioid receptor antagonists (e.g., nalmefene), respiratory stimulants, and buprenorphine. None of these approaches target polysubstance overdose and only one novel approach (a wearable naloxone delivery device) would address the narrow treatment window.

Prevalence and duration of prescribed opioid use during pregnancy: a cohort study from the Quebec Pregnancy Cohort

BackgroundRecent studies show a rapid growth among pregnant women using high potency opioids for common pain management during their pregnancy. No study has examined the duration of treatment among strong opioid users and weak opioid users during pregnancy. We aimed to investigate the prevalence of prescribed opioid use during pregnancy, in Quebec; and to compare the duration of opioid treatment between strong opioid users and weak opioid users.MethodsUsing the Quebec Pregnancy Cohort (1998–2015), we included all pregnancies covered by the Quebec Public Prescription Drug Insurance Program. Opioid exposure was defined as filled at least one prescription for any opioid during pregnancy or before pregnancy but with a duration that overlapped the beginning of pregnancy. Prevalence of opioids use was calculated for all pregnancies, according to pregnancy outcome, trimester of exposure, and individual opioids. The duration of opioid use during pregnancy was analyzed according to 8 categories based on cumulative duration (< 90 days vs. ≥90 days), duration of action (short-acting vs. long-acting) and strength of the opioid (weak vs. strong).ResultsOf 442,079 eligible pregnancies, 20,921 (4.7%) were exposed to opioids. Among pregnancies ending with deliveries (n = 249,234), 5.4% were exposed to opioids; the prevalence increased by 40.3% from 3.9% in 1998 to 5.5% in 2015, more specifically a significant increase in the second and third trimesters of pregnancy. Weak opioid, codeine was the most commonly dispensed opioid (70% of all dispensed opioids), followed by strong opioid, hydromorphone (11%), morphine (10%), and oxycodone (5%). The prevalence of codeine use decreased by 47% from 4.3% in 2005 to 2.3% in 2015, accompanied by an increased use of strong opioid, morphine (0.029 to 1.41%), hydromorphone (0.115 to 1.08%) and oxycodone (0.022 to 0.44%), from 1998 to 2015. The average durations of opioid exposure were significantly longer among pregnancies exposed to strong opioid as compared to weak opioid regardless of the cumulative duration or duration of action (P < 0.05).ConclusionsGiven the differences in the safety profile between strong opioids and the major weak opioid codeine, the increased use of strong opioids during pregnancy with longer treatment duration raises public health concerns.

Medications and risk of motor vehicle collision responsibility in British Columbia, Canada: a population-based case-control study

Many medications impair driving skills yet their influence on collision risk remains uncertain. We aimed to systematically investigate the risk of collision responsibility associated with common classes of prescription medications. In this population-based case-control study we analysed linked driving and health records in British Columbia, Canada from Jan 1, 1997, to Dec 31, 2016. The study cohort included all drivers involved in an incident collision (defined as first collision after 3 collision-free years) that resulted in a police report. We scored police collision reports and classified drivers as responsible for the collision (cases) or not responsible (controls); drivers with indeterminate scores were excluded. We used logistic regression to determine odds of collision responsibility in drivers with current prescriptions for medications of interest versus drivers without prescriptions. To explore whether risk of collision responsibility was related to medication effect or driver factors, we compared risk in current medication users versus past users. To study whether drivers developed tolerance to medication effects, we compared risk in new (first 30 days of a prescription) versus established users. During the study period, 4 906 925 drivers had their driving licence linked to health records; of these drivers, 747 662 unique drivers were involved in 837 919 incident collisions between Jan 1, 2000, and Dec 31, 2016. 382 685 drivers responsible for the collision (cases) and 332 259 drivers not responsible (controls) were included in the final analysis; 122 975 drivers with indeterminate responsibility were excluded. We found increased risk of collision responsibility in drivers prescribed sedating antipsychotics (adjusted odds ratio [aOR] 1·35 [98·75% CI 1·25-1·46]), long-acting benzodiazepines (aOR 1·30 [1·22-1·38]), short-acting benzodiazepines (aOR 1·25 [1·20-1·31]), and high-potency opioids (aOR 1·24 [1·17-1·30]). Among medications used for medical indications, the highest risk was seen in drivers prescribed neurological medications: cholinergic drugs (aOR 1·83 [1·39-2·40]), anticholinergic agents for Parkinson's disease (aOR 1·45 [1·08-1·96]), dopaminergic agents (aOR 1·20 [1·04-1·38]), and anticonvulsants (aOR 1·20 [1·14-1·26]). People currently taking benzodiazepines, non-sedating antidepressants, high-potency opioids, and anticonvulsants had increased risk compared with past users, and we did not find increased risk in new compared with established users of these drugs. Drivers prescribed benzodiazepines or high-potency opioids are at increased risk of being responsible for collisions and this risk does not decrease over time. Several other classes of medications are associated with increased risk, but this association might be independent of medication effect. These findings can guide medication warnings and prescription choices and inform public education campaigns targeting impaired driving. Canadian Institutes of Health Research.

Regional Differences in Opioid Prescribing in Germany - Results of an Analysis of Health Insurance Data of 57 Million Adult People.

BackgroundRegional variations of opioid use have been reported from many countries. The objective of this study was to examine opioid prescribing patterns in Germany including low- and high-potency opioids (LPO and HPO) focusing on regional differences.MethodsData source was the “Information system for health care data” comprising statutory health insurance funds data for about 70 million Germans of all ages. For 2010, we received aggregated data (by age, sex, federal state and district) of Germans (18+) who had been prescribed at least one opioid including the number of prescribed packages. For each stratum, we further received the number of insured persons. We calculated LPO and HPO prevalences and the mean number of prescribed packages.ResultsAmong 57 million adult Germans (mean age: 50.2 years, 53.8% female), opioid prevalences were 38.7 per 1000 persons for LPOs and 12.8 for HPOs. Prevalences rose with increasing age and were higher in women than in men. On average, LPO users were prescribed fewer packages than HPO users (3.5 vs 7.0). LPO use was highest in the eastern states ranging from 32.9 per 1000 persons (Hamburg) to 47.2 (Saxony-Anhalt). HPOs were most often prescribed in the North and in the East with prevalences varying between 10.6 per 1000 persons (Baden-Württemberg) and 16.9 (Mecklenburg-Western Pomerania). On the district level, prevalences varied by the factors 2.6 and 3.2 for LPOs and HPOs, respectively.ConclusionWe found large regional variations in opioid prescribing which probably cannot only be attributed to differences in patient characteristics.

Oxycodone, Hydromorphone, and the Risk of Suicide: A Retrospective Population-Based Case-Control Study.

Opioids have been increasingly associated with suicide, but whether they are independent contributors is unclear. Oxycodone and hydromorphone are commonly prescribed high-potency opioids that can differentially affect mood. The objective of this study was to explore whether oxycodone and hydromorphone are differentially associated with suicide. We conducted a retrospective population-based case-control study in Ontario, Canada, from 1992 to 2014. Using coronial data, we defined case subjects as individuals who died by suicide involving an opioid overdose. Each of these was matched with up to four controls who died of accidental opioid overdose. We ascertained exposure to oxycodone, hydromorphone, and other opioids from postmortem toxicology testing. We used odds ratios and 95% confidence intervals to examine whether opioid-related suicide was disproportionately associated with oxycodone relative to hydromorphone. We identified 438 suicides and 1212 accidental deaths, each of which involved either oxycodone or hydromorphone but not both. The median age at death was 49years and 51% were men. After adjusting for a history of self-harm, psychiatric illness, and exposure to other opioids, we found that oxycodone was more strongly associated with suicide than hydromorphone (adjusted odds ratio 1.59; 95% confidence interval 1.20-2.11). In a secondary analysis, we observed a trend of similar magnitude in which combined exposure to oxycodone and hydromorphone was more strongly associated with suicide than hydromorphone alone (adjusted odds ratio 1.68; 95% confidence interval 0.92-3.09). While preliminary, these findings support the possibility that some high-potency opioids might independently influence the risk of suicide in susceptible individuals.

Does Surgical-site Multimodal Drug Injection After Palmar Plating of Distal Radius Fractures Improve Pain Scores?

Does Surgical-site Multimodal Drug Injection After Palmar Plating of Distal Radius Fractures Improve Pain Scores?

Regulatory and other responses to the pharmaceutical opioid problem.

In the last twenty years there have been substantial increases in the use of pharmaceutical opioids in many countries, including Australia which has one of the highest levels of opioid utilisation globally 1. Almost 15 million opioid prescriptions were dispensed in 2015 and our use of high-potency opioids has also increased 2. One of the main drivers is the increased use of prescription opioids for chronic non-caner pain (CNCP) 3. In parallel to escalating use, opioid-related harms have also increased. Since 2000, there has been a shift in both hospitalisations due to opioid poisonings and opioid-related deaths, from predominantly heroin to pharmaceutical opioids4. Use pharmaceutical opioids for non-medical purposes is also relatively common, reported by 4.8% of the Australian population4. A range of possible strategies to minimise unnecessary opioid exposure and adverse events were highlighted in the National Pharmaceutical Drug Misuse Framework for Action (2012–2015) 5 including: coordinated medication management systems (prescription drug monitoring programmes (PDMPs); improvement of access to pain and addiction services; development of resources, and workforce development. To date, few of these strategies have been implemented. We summarise recent and emerging responses in Australia that aim to minimise harms from pharmaceutical opioids. Regulatory responses aimed at reducing aberrant opioid prescribing and restricting opioid supply Codeine rescheduling In 2016, the most common analgesics used for non-medical purposes by Australians were over-the-counter (OTC) codeine products4. There have been several attempts to reduce extra medical use and harms from OTC codeine. In May 2010, OTC codeine products were up-scheduled from Schedule 2 (Pharmacy Medicine) to Schedule 3 (Pharmacist Only Medicine). This change, however, had no meaningful impact on codeine poisonings 6. They were subsequently up-scheduled again in February 2018 to Schedule 4 (Prescription-only medicines). The impacts of this decision remain to be seen 7.

Urine drug screening for early detection of unwitting use of fentanyl and its analogues among people who inject heroin in Sydney, Australia.

North America has witnessed a dramatic rise in fatal opioid overdoses due to the unwitting consumption of non-pharmaceutical fentanyl and its analogues. While some of the drivers of this crisis-including profitability and access to high-potency opioids through internet sources-also apply in Australia, to our knowledge, there have been no ongoing surveillance studies of local populations. Therefore, this pilot study aimed to detect unintentional fentanyl consumption among people who inject heroin through instant urine screening, and determine the feasibility and acceptability of voluntary urinalysis of clients at the Medically Supervised Injecting Centre, Kings Cross, Sydney. Brief surveys and urine drug screens were conducted with 67 participants in Wave 1 (October 2017) and 51 participants in Wave 2 (March 2018). Urine samples were tested with BTNX Rapid Response™ fentanyl urine strip test at a detection level of 20 ng/mL norfentanyl. These strips also cross-react to numerous fentanyl analogues. There were no cases where positive urine tests suggested unwitting fentanyl use detected in this study. These negative findings contrast sharply with similar Canadian studies. While no cases of fentanyl-laced heroin use have been detected so far, we have demonstrated that this surveillance design is low-cost, feasible and scalable approach to monitoring the considerable public-health threat of undetected fentanyl and its analogues in Australia. Further validation of cross-reactivity of test strips would strengthen this method.

Trends in and predictors of hydromorphone administration in US emergency departments (2007-2014).

To examine recent trends in and predictors of hydromorphone administration in US emergency departments (EDs) compared with other opioids. Retrospective review of data from the National Hospital Ambulatory Medical Care Survey from 2007 to 2014. All adult ED visits where an opioid analgesic was administered were included. Trends in and predictors of hydromorphone administration were assessed using survey-weighted logistic regression, comparing hydromorphone visits with ED visits where other opioids were administered. From 2007 to 2014, in an estimated 128.9 million US ED visits where opioids were administered, hydromorphone use increased significantly from 30.2 percent in 2007 to 36.8 percent of visits in 2014 (p = 0.027). Hydromorphone accounted for a greater proportion of opioids administered by the end of the study period, compared to other opioids. Patient characteristics associated with hydromorphone were age <65 years, white race, private insurance or Medicare, and severe pain. Patients who received hydromorphone also had indicators of higher severity illness, including more laboratory testing, procedures, and higher admission rates. Common conditions where hydromorphone was administered were headache, back pain, musculoskeletal pain, and abdominal pain. From 2007 to 2014, hydromorphone was administered to more than one in three US ED patients who were administered opioids, and several factors predicted its use. High use was found in some conditions where opioid use is inappropriate, suggesting a need for additional initiatives to promote rational prescribing of high-potency opioids.

A Novel Oral Fluid Assay (LC-QTOF-MS) for the Detection of Fentanyl and Clandestine Opioids in Oral Fluid After Reported Heroin Overdose.

The adulteration of heroin with non-pharmaceutical fentanyl and other high-potency opioids is one of the factors contributing to striking increases in overdose deaths. To fully understand the magnitude of this problem, accurate detection methods for fentanyl and other novel opioid adulterant exposures are urgently required. The objective of this work was to compare the detection of fentanyl in oral fluid and urine specimens using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) in a population of heroin users presenting to the Emergency Department after overdose. This was a prospective observational study of adult Emergency Department patients who presented after a reported heroin overdose requiring naloxone administration. Participants provided paired oral fluid and urine specimens, which were prepared, extracted, and analyzed using a dual LC-QTOF-MS workflow for the identification of traditional and emerging drugs of abuse. Analytical instrumentation included SCIEX TripleTOF® 5600+ and Waters Xevo® G2-S QTOF systems. Thirty participants (N=30) were enrolled during the study period. Twenty-nine participants had fentanyl detected in their urine, while 27 had fentanyl identified in their oral fluid (overall agreement 93.3%, positive percent agreement 93.1%). Cohen's Kappa (k) was calculated and demonstrated moderately, significant agreement (k=0.47; p value 0.002) in fentanyl detection between oral fluid and urine using this LC-QTOF-MS methodology. Additional novel opioids and metabolites, including norfentanyl, acetylfentanyl, and U-47700, were detected during this study. In this study of individuals presenting to the ED after reported heroin overdose, a strikingly high proportion had a detectable fentanyl exposure. Using LC-QTOF-MS, the agreement between paired oral fluid and urine testing for fentanyl detection indicates a role for oral fluid testing in surveillance for nonpharmaceutical fentanyl. Additionally, the use of LC-QTOF-MS allowed for the detection of other clandestine opioids (acetylfentanyl and U-47700) in oral fluid.

Long-term treatment in chronic noncancer pain: Results of an observational study comparing opioid and nonopioid therapy

Background and aimsRecent studies reveal high prevalence rates of patients receiving long-term opioids. However, well designed studies assessing effectiveness with longer than 3 months follow-up are sparse. The present study investigated the outcomes of long-term opioid therapy compared to nonopioid treatment in CNCP patients with respect to measures of pain, functional disability, psychological wellbeing, and quality of life (QoL). MethodsThree hundred and thirty three consecutive patients at our pain clinic were included and divided into patients with continuous opioid treatment for at least 3 months (51%) and patients receiving nonopioid analgesics (49%). Further, outcome of different doses of opioid (<120mg vs. >120mg morphine equivalents) and differences between high and low potency opioids were examined. ResultsThe opioid and nonopioid groups did not differ with regard to pain intensity or satisfaction with analgesic. Patients with continuous opioids treatment reported higher neuropathic like pain, longer duration of pain disorder, lower functional level, wellbeing, and physical QoL in comparison to patients receiving nonopioid analgesics. Higher opioid doses were associated with male gender, intake of high potency opioids and depression but there were no differences with regard to pain relief or improvement of functional level between high and low doses. Similarly, patients on high potency opioids reported more psychological impairment than patients on low potency opioids but no advantage with regard to pain relief. Overall, remaining level of pain, functional disability and poor QoL were quite high irrespective of the analgesic used or opioid dosing. ConclusionIn the long-term no clear advantage of opioid vs. non-opioid analgesics could be revealed. In terms of remaining pain intensity, functional disability and quality of life, treatment with pain medication proved insufficient. Additionally, with higher doses of opioids the benefit to risk relationship becomes worse and patients on high potency opioids reported more psychological impairment than patients on low potency opioids but no advantage with regard to pain relief. ImplicationsOur results raise questions about the long-term effectiveness of analgesic treatment regimens irrespective of analgesics type employed and call for more multidisciplinary treatment strategies.

LO11: Opiate prescribing in Ontario emergency departments

Introduction: Increased prescribing of high potency opioids has been associated with increasing opioid addiction and linked to serious adverse outcomes including misuse, diversion, overdose and death. Problems related to opioids are a major Canadian public health concern yet few data are available on prescribing in most Canadian provinces. The objective of this study was to describe opioid prescribing in Ontario EDs and patient harms associated with this practice. Methods: We conducted a population-based cohort study among Ontario residents aged 15-64 years who were eligible for public drug coverage between April 2008 and March 2012. Using administrative databases, we identified patients with no opioid use in the past 12 months who received a prescription opioid from an emergency or family physician. Patients were followed for 2 years following their index prescription. The primary outcome was hospital admission for opioid toxicity and secondary outcome was dose-escalation exceeding 200 mg morphine equivalents (MEQ). Results: Of the 77,270 unique patients included, 33,492 (43.3%) and 43,778 (56.7%) prescriptions were issued by emergency physician (EP) and family physicians (FP), respectively. FP patients were older (45.9 vs 41.2 yr, MSD 0.35), had fewer ED visits (0.9 vs 2.3, MSD 0.46), and more FP visits (11.5 vs 8.7 MSD 0.31) in the year prior to their index visit. For combination products, EPs were more likely to prescribe oxycodone compared to FPs (37.2% vs 16.7%, Δ 20.5, 95% CI: 19.9, 21.2). For single agent products, EPs were more likely to prescribe hydromorphone compared to FPs (44.5% vs 21.7%, Δ 22.8, 95% CI: 20.4, 25.2). FPs were more likely to prescribe codeine either as a combination or single agent formulation. EP prescriptions led to significantly more hospital admissions for opioid toxicity (0.5% vs 0.3%, Δ 0.2, 95% CI: 0.1, 0.3), while FP prescriptions more often resulted in dose escalation beyond 200 mg MEQs (0.1% vs 0.7%, Δ 0.6, 95% CI: 0.4, 0.7). Conclusion: A large percentage of opioid-naïve patients receive an initial opiate prescription in the ED, where the use of high potency opioids is much more common, with 1/200 of these patients subsequently hospitalized for opioid toxicity. Creation of a physician accessible provincial registry would be useful to monitor opioid prescribing and dispensing, inform clinical practice, and identify patients at high-risk who may benefit from early interventions.

Perioperative management of opioid-tolerant patients

### Key points The assessment and treatment of opioid-tolerant patients in the perioperative and postoperative period can be challenging. Acute pain management can often be inadequate due to a number of factors. Compared with opioid-naive patients, opioid-tolerant patients will typically generate a greater workload for medical and nursing staff. Opioid tolerant patients express higher rest and dynamic pain scores, and two to three times greater opioid use via patient-controlled analgesia (PCA). They require more frequent consultations and prescription alterations.1 Medical and nursing staff may be unaccustomed to managing such patients and may be apprehensive in prescribing or administering large doses of opioids because of a fear of causing harm. Under-treatment of pain may result in opioid-seeking behaviour with the patient perceived as ‘manipulative’ and ‘non-cooperative’. This can have a negative impact on the doctor–patient relationship and overall patient care. Therefore the pain management plan for opioid tolerant patients requires careful consideration in the perioperative period in order to (i) prevent opioid withdrawal, (ii) provide effective analgesia, and (iii) to ensure continuity of care in the community after discharge from hospital. This review considers the various strategies that can be used in such settings. Opioids are prescribed to treat pain from a variety of causes, including chronic non-cancer pain, cancer pain, acute pain, and as substitution therapy in …

The Risk of Ischemic Cardio- and Cerebrovascular Events Associated with Oxycodone-Naloxone and Other Extended-Release High-Potency Opioids: A Nested Case-Control Study.

In Germany, an extended-release (ER) combination of the high-potency opioid (HPO) oxycodone and the antagonist naloxone was approved in 2006. In recent years, the cardio- and cerebrovascular safety of opioid antagonists and of opioids themselves has been discussed. The objective of this study was to estimate the risk of major ischemic cardio- and cerebrovascular events in patients receiving ER oxycodone-naloxone compared with those receiving other ER HPOs. We used the German Pharmacoepidemiological Research Database (GePaRD) to conduct a nested case-control study (2006-2011) within a cohort of ER HPO users. Cases were defined as patients hospitalized for acute myocardial infarction (MI) or ischemic stroke (IS). For each case, up to ten controls were selected by risk-set sampling. Using conditional logistic regression, confounder-adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were obtained for the risk of MI/IS associated with (1) current HPO treatment, (2) recent discontinuation, or (3) recent switch of HPO therapy compared with past treatment. In 309,936 ER HPO users, 12,384 MI/IS events were detected, resulting in a crude incidence rate of 19.48 (95% CI 19.14-19.82) per 1000 person years. A small but significantly elevated aOR was found for morphine (1.12; 95% CI 1.04-1.22) but not for oxycodone-naloxone. Recent discontinuation and recent switch of any ER HPO also had a significant impact on the outcome (aOR 1.12; 95% CI 1.04-1.21 and 1.25; 95% CI 1.03-1.52, respectively). Our study does not indicate an association between oxycodone-naloxone and ischemic cardio- or cerebrovascular events. However, our findings do suggest that every change in ER HPO therapy should be conducted with caution.

Adequacy of pain management in oncology patients at a tertiary hospital in Ghana

Background: Although cancer pain is well documented, efficient management is largely inadequate in most patients especially in developing countries. This study evaluated the adequacy of pain management as well as potential social factors that may be associated with inadequate pain management.Methods: 204 ambulatory oncology patients (82% female; mean age 53.5) attending clinic at the Oncology Directorate, of a tertiary hospital in Ghana from January to December, 2015 were recruited and their pain severity and functional interference assessed with the Brief Pain Inventory (BPI). The adequacy of pain management was computed as the pain management index (PMI) using the BPI.Results: Although 62% of respondents were prescribed high potency opioids, 56.9% of them exhibited significant pain while 34.9% required a stronger analgesic to manage their pain. Majority of patients (56%) were over-managed for their pain (had PMI score &gt;0). Only 26.4% had optimal cancer pain management. Pain interfered mostly with patients’ sleep (46.2%) and general activity (42.5%). Patients with high pain intensity were more likely to have it affect their daily activity (P&lt;0.0001). Men were more likely to have inadequate pain management than females.Conclusions: This study has shown that whereas pain management may be adequate, there is the tendency for opioid tolerance and abuse as over 50% of patients receive more analgesics than required. The tenets of the WHO 3-step analgesic ladder should be strictly adhered to achieve optimum cancer pain relief.

The dark side of opioids in pain management: basic science explains clinical observation.

In the past 2 decades, opioids have been used increasingly for the treatment of persistent pain, and doses have tended to creep up. As basic science elucidates mechanisms of pain and analgesia, the cross talk between central pain and opioid actions becomes clearer. We aimed to examine the published literature on basic science explaining pronociceptive opioid actions, and apply this knowledge to clinical observation. We reviewed the existing literature on the pronociceptive actions of opioids, both preclinical and clinical studies. Basic science provides a rationale for the clinical observation that opioids sometimes increase rather than decrease pain. Central sensitization (hyperalgesia) underlies pain chronification, but can also be produced by high dose and high potency opioids. Many of the same mechanisms account for both central pain and opioid hyperalgesia. Newly revealed basic mechanisms suggest possible avenues for drug development and new drug therapies that could alter pain sensitization through endogenous and exogenous opioid mechanisms. Recent changes in practice such as the introduction of titration-to-effect for opioids have resulted in higher doses used in the clinic setting than ever seen previously. New basic science knowledge hints that these newer dosing practices may need to be reexamined. When pain worsens in a patient taking opioids, can we be assured that this is not because of the opioids, and can we alter this negative effect of opioids through different dosing strategies or new drug intervention?