Clinical Consumption of Opioid Analgesics in China: A Retrospective Analysis of the National and Regional Data 2006–2016

ContextThe annual consumption of opioid analgesics in the U.S. was more than 10 times the world average, whereas that in China was at a moderate level within Asia but much lower than the worldwide average. The opposite situations of opioid use in the U.S. and China revealed totally different problems in the developed versus developing world, that is, overuse versus underuse of opioids.ObjectivesThis study analyzed the clinical consumption, estimated the needs of pain treatment, and evaluated the adequacy of opioid analgesic consumption in mainland China and its seven regions.MethodsA retrospective analysis of the national and regional consumption of opioid analgesics in mainland China during 2006–2016 was conducted. The adequacy of consumption measure was used to gauge the overall adequacy of opioid analgesic consumption in morphine equivalents (MEs) for the treatment of moderate-to-severe pain in mainland China and compared with international data. Annual per capita consumption was adopted to measure the clinical consumption of opioid analgesics in MEs at a national level and across seven regions of mainland China. Needs of morphine for cancer pain treatment in mainland China and in its seven regions were estimated and compared with the clinical consumption of opioid analgesics in MEs.ResultsThe adequacy of consumption measure of mainland China ranged from 0.0041 to 0.0088 during 2006–2016, which was less than 1% of that in the reference countries. The poor North East region had only 10.85% of the cancer pain morphine needs fulfilled. The highest fulfillment rate was 36.02% in rich Southern China, which was 25.9% at the national level.ConclusionThe clinical consumption of opioid analgesics for the treatment of moderate-to-severe pain in mainland China was far below the international level. The annual per capita of clinical consumption was lower, and the adequacy of cancer pain treatment was poorer in less developed areas. All these findings call for actions to strengthen pain management.     

The Medical Consumption of Opioids in Colombia, 1997–2007

ABSTRACT

The World Health Organization classifies opioid analgesics as essential medicines in the treatment of severe pain and recommends their increased availability. The combination of availability, training of professionals, and a legal framework granting access to these medicines has led to a sharp increase in the consumption of morphine and other opioids in developed countries. However, in Colombia, consumption of opioid analgesics appears to fail to meet patient needs. To analyze the current trends in medical consumption of opioids in Colombia, the numbers of defined daily doses of opioid analgesics for total inhabitants and the population that died of cancer between 1997 and 2007 were calculated and compared. The import of raw materials and medicines varied greatly every year. However, from 2003, a trend toward the increased consumption of morphine, hydromorphone, and methadone was observed. Availability was inconsistent and opioid consumption showed an increase when calculated for total inhabitants and for cancer deaths. The unreliable availability of opioid analgesics may be responsible for their limited consumption. Chronic underuse and a trend toward increased consumption have been confirmed. Monitoring of consumption to promote rational use is recommended.     

What do different databases tell about the use of opioids in seven European countries in 2002?

Objective: The objective of this paper was to analyse opioid consumption in a number European countries using different sources of data. Methods: Data were extracted from the United Nations’ International Narcotics Control Board Report (INCB) 2003 and from the registers of the national health authorities in seven countries where data were available for 2002. The amount of opioid used was calculated as daily defined doses per 1000 inhabitants per day (DDD/1000/day). Danish Register of Medicinal Products Statistics was further explored for characteristics of opioid consumption (age, gender, type of opioids consumed) by patients in primary care. Total opioid consumption and consumption of 11 selected opioids (7 strong and 4 weak) were analysed. The amount of opioids consumed by outpatients was also examined. Results: There were considerable differences in the number of opioids reported and significant discrepancies in the amounts of opioids consumed between the national data and the INCB report. The source of data for the national registers on drug consumption varied (pharmacies or wholesale). The INCB data provide information on opioid import and estimated need rather than on medical consumption. Conclusions: Caution is required when interpreting the data on opioid consumption between countries because of differences in the collection and reporting of data. Better recording of opioid consumption is needed for meaningful analysis of opioid consumption and its possible effect on pain management in different countries. Data on opioids consumed for cancer‐related pain in comparison with chronic non‐malignant pain are needed. A uniform method of collection of data on analgesic consumption should be established for all European countries.     

A First Comparison Between the Consumption of and the Need for Opioid Analgesics at Country,Regional, and Global Levels

ABSTRACT

The objective of this study was to propose a rough but simple method for estimating the total population need for opioids for treating all various types of moderate and severe pain at the country, regional, and global levels. We determined per capita need of strong opioids for pain related to three important pain causes for 188 countries. These needs were extrapolated to the needs for all the various types of pain by using an adequacy level derived from the top 20 countries in the Human Development Index. By comparing with the actual consumption levels for relevant strong opioid analgesics, we were able to estimate the level of adequacy of opioid consumption for each country. Good access to pain management is rather the exception than the rule: 5.5 billion people (83% of the world's population) live in countries with low to nonexistent access, 250 million (4%) have moderate access, and only 460 million people (7%) have adequate access. Insufficient data are available for 430 million (7%). The consumption of opioid analgesics is inadequate to provide sufficient pain relief around the world. Only the populations of some industrialized countries have good access. Policies should seek a balance between maximizing access for medical use and minimizing abuse and dependence. Countries should aim to increase the medical consumption to the magnitude needed to address the totality of moderate and severe pain.     

The medical consumption of opioids in Colombia, 1997-2007

The World Health Organization classifies opioid analgesics as essential medicines in the treatment of severe pain and recommends their increased availability. The combination of availability, training of professionals, and a legal framework granting access to these medicines has led to a sharp increase in the consumption of morphine and other opioids in developed countries. However, in Colombia, consumption of opioid analgesics appears to fail to meet patient needs. To analyze the current trends in medical consumption of opioids in Colombia, the numbers of defined daily doses of opioid analgesics for total inhabitants and the population that died of cancer between 1997 and 2007 were calculated and compared. The import of raw materials and medicines varied greatly every year. However, from 2003, a trend toward the increased consumption of morphine, hydromorphone, and methadone was observed. Availability was inconsistent and opioid consumption showed an increase when calculated for total inhabitants and for cancer deaths. The unreliable availability of opioid analgesics may be responsible for their limited consumption. Chronic underuse and a trend toward increased consumption have been confirmed. Monitoring of consumption to promote rational use is recommended.     

The role of methadone in cancer pain treatment – a review

Background: Methadone is an opioid analgesic of step 3 of the World Health Organization (WHO) analgesic ladder. Aim and Methods: To outline pharmacodynamics, pharmacokinetics, drug interactions, equianalgesic dose ratio with other opioids, dosing rules, adverse effects and methadone clinical studies in patients with cancer pain. A review of relevant literature on methadone use in cancer pain was conducted. Results: Methadone is used in opioid rotation and administered to patients with cancer pain not responsive to morphine or other strong opioids when intractable opioid adverse effects appear. Methadone is considered as the first strong opioid analgesic and in patients with renal impairment. Methadone possesses different pharmacodynamics and pharmacokinetics in comparison to other opioids. The advantages of methadone include multimode analgesic activity, high oral and rectal bioavailability, long lasting analgesia, lack of active metabolites, excretion mainly with faeces, low cost and a weak immunosuppressive effect. The disadvantages include long and changeable plasma half‐life, high bound to serum proteins, metabolism through P450 system, numerous drug interactions, lack of clear equianalgesic dose ratio to other opioids, QT interval prolongation, local reactions when administered subcutaneously. Conclusions: Methadone is an important opioid analgesic at step 3 of the WHO analgesic ladder. Future controlled studies may focus on establishment of methadone equianalgesic dose ratio with other opioids and its role as the first strong opioid in comparative studies with analgesia, adverse effects and quality of life taken into consideration.     

Adequacy of Opioid Analgesic Consumption at Country,Global, and Regional Levels in 2010, Its Relationship With Development Level,and Changes Compared With 2006

ContextIn most countries, patients do not have adequate access to opioid analgesics because of barriers resulting from the abuse potential of these medicines.ObjectivesTo provide an analysis for the adequacy of the consumption of opioid analgesics for countries and World Health Organization regions in 2010 as compared with 2006.MethodsWe calculated the Adequacy of Consumption Measure using data for 2010 based on a method established by Seya et al. This method calculates the morbidity-corrected needs per capita for relevant strong opioid analgesics and the actual use for the top 20 Human Development Index countries. It determines the adequacy of the consumption for each country, World Health Organization region, and the world by comparing the actual consumption with the calculated need. Furthermore, the method allows us to calculate the number of people living in countries at various levels of adequacy. We compared our outcomes with data from Seya et al. for 2006.ResultsMost people have no access to opioids for pain relief in case of need; 66% of the world population has virtually no consumption, 10% very low, 3% low, 4% moderate, and only 7.5% adequate. For 8.9%, no data are available. Between 2006 and 2010, 67 countries increased the adequacy of opioid consumption per capita. These changes are independent of countries' level of development.ConclusionThe consumption of opioid analgesics remains inadequate in most of the world and, as a result, patients with moderate and severe pain do not receive the treatment they need. Governments, health organizations, and nongovernmental organizations must collaborate to address this situation, targeting their efforts at educational, cultural, health policy and regulatory levels.     

Opioid Use in the Philippines – 20 years after the introduction of the WHO analgesic ladder

AimTo find out if the opioid usage has improved in the Philippines 20 years after the introduction of the WHO analgesic ladder.BackgroundTwenty years after the introduction of the WHO analgesic ladder in the Philippines, usage of morphine for cancer pain relief is still low. Barriers to opioid prescribing persist because of factors attributable to physicians, patients, families and constraints imposed by government regulatory bodies.MethodsA survey of 211 physicians on a purposive sampling representing various regions in the country was done. Respondents included anesthesiologists, surgeons, oncologists, and palliative care specialists, who were expected to prescribe opioids in their practice. A 20-item multiple-choice questionnaire was developed to explore possible barriers to opioid prescribing.ResultsThere is a very good awareness of the WHO analgesic ladder (72%) as well as the availability of opioids in their areas of practice (89.57%). Monitoring of pain as the “fifth vital sign” is adhered to by 68.25% of the respondents. There was only 60.66% compliance regarding availment of a narcotics license among respondent physicians. Various reasons were identified as to why they failed to get a narcotics license.ConclusionsThere was adequate knowledge about the WHO analgesic ladder among the respondents. There is a perceived resistance to prescribe strong opioids like morphine making the step 2 of the ladder as a comfort zone by the physicians who tend to “overstay” in this step. Government regulatory policies have affected the physicians' attitudes concerning narcotics license application. There is a very slow, though steady increase in morphine and oxycodone usage in the country. Barriers to opioid use in cancer pain management still persist twenty years after the introduction of the WHO analgesic ladder.     

Patterns of opioid use for chronic noncancer pain in the Veterans Health Administration from 2009 to 2011

Although opioids are frequently prescribed for chronic noncancer pain (CNCP) among Veterans Health Administration (VHA) patients, little has been reported on national opioid prescribing patterns in the VHA. Our objective was to better characterize the dosing and duration of opioid therapy for CNCP in the VHA. We analyzed national VHA administrative and pharmacy data for fiscal years 2009 to 2011. For individuals with CNCP diagnoses and any opioid use in the fiscal year, we calculated the distribution of individual mean daily opioid dose, individual total days covered with opioids in a year, and individual total opioid dose in a year. We also investigated the factors associated with being in the top 5% of individuals for total opioid dose in a year, which we term receipt of high-volume opioids. About half of the patients with CNCP received opioids in a given fiscal year. The median daily dose was 21 mg morphine equivalents. Approximately 4.5% had a mean daily dose higher than 120 mg morphine equivalents. The median days covered in a year was 115 to 120 days in these years for those receiving opioids. Fifty-seven percent had at least 90 days covered with opioids per year. Major depression and posttraumatic stress disorder were positively associated with receiving high-volume opioids, but nonopioid substance use disorders were not. Among VHA patients with CNCP, chronic opioid therapy occurs frequently, but for most patients, the average daily dose is modest. Doses and duration of therapy were unchanged from 2009 to 2011.     

The Effects of Opioids on Cognition in Older Adults With Cancer and Chronic Noncancer Pain: A Systematic Review

ContextOpioids are prescribed to manage moderate-to-severe pain and can be used with older adults; however, they may lead to several adverse effects, including cognitive impairment.ObjectivesTo identify, appraise, and synthesize evidence on the impact of opioids on cognition in older adults with cancer/chronic noncancer pain, and screening tools/neuropsychological assessments used to detect opioid-induced cognitive impairment.MethodsA systematic literature review following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (international prospective register of systematic reviews registration: CRD42018092943). MEDLINE, EMBASE, PsycINFO, CINAHL, Cochrane Library, and Web of Science were searched up to December 2018. Randomized controlled trials, quasi-experimental studies, and observational studies of adults aged 65 years and older with cancer/chronic noncancer pain taking opioids were included. A narrative synthesis was conducted.ResultsFrom 4036 records, 10 met inclusion criteria. Five studies used one screening tool, and five studies used a range of neuropsychological assessments; assessing 14 cognitive domains. Most studies demonstrated no effect of opioid use on cognitive domains, whereas four studies showed mixed effects. In particular, attention, language, orientation, psychomotor function, and verbal working/delayed episodic memory were worsened. Changes to cognitive function were predominantly observed in studies with higher mean doses of opioids (120–190.7mg oral morphine equivalent daily dose).ConclusionBoth improvements and impairments to cognition were observed in studies with higher mean opioid doses. In clinical practice, a brief screening tool assessing attention, language, orientation, psychomotor function, and verbal working/delayed episodic memory may be beneficial to detect worsening cognition in older adults with chronic pain using opioids.     

Long-term intrathecal morphine influence on major compounds of the endocrine system in elderly population

BackgroundThe influence of long-term opioid administration on hormonal levels is not well characterized in the literature. We previously showed that intrathecal opioid therapy significantly influences the homeostasis of immune and endocrine systems. Other authors confirmed that exogenous and endogenous opioids induce this effect. They have a cytokine-like behavior and may function as neurotransmitters, neuromodulators or hormones, as concerning their synthesis, storage and release.AimsTo assess the effects of morphine long-term intrathecal administration on serum levels of Gonadal, Thyroidal and Adrenal axis hormones in an elderly population affected by chronic pain; to assess the correlation between hormone levels and morphine dosage.MethodsPatients suffering from chronic non-cancer pain with or without intrathecal drug delivery system were studied and hormonal levels were monitored, using an immunoradiometric assay kit.ResultsThe long-term administration of intrathecal morphine influenced part of the endocrine system, in particular, there was a reduction of FSH and LH and an increment of GH serum levels; this effect was morphine dose dependent.ConclusionLong-term intrathecal opioid administration influenced FSH, LH and GH serum levels. Data on this issue are inadequately described in the literature. The finding of endocrine effects of opioid therapy, nonetheless, cannot be ignored, as it may have clinical relevance in both elderly and young population. We believe that during long intrathecal pain treatments with morphine, clinicians should be aware of both immediate and later opioids side effects, and in particular, they should monitor immune and endocrine changes.     

The effects of a morphine shortage on emergency department pain control

ObjectiveIn 2018, due to a national morphine shortage, our two study emergency departments (EDs) were unable to administer intravenous (IV) morphine for over six months. We evaluated the effects of this shortage on analgesia and patient disposition.MethodsThis was a retrospective study in two academic EDs. Our control period (with morphine) was 4/1/17–6/30/17 and our study period (without morphine) was 4/1/18–6/30/18. We included all adult patients with a chief complaint of pain, initial pain score ≥4, and ≥2 recorded pain scores. The primary outcome was delta pain score. Secondary outcomes included final pain score, proportion of ED visits with opioids vs. non-opioids administered, and ED disposition.ResultsWe identified 6296 patients during our control period and 5816 during our study period. There was no significant difference in mean final pain score (study 4.45, control 4.44, p = 0.802), delta pain score (study −3.30, control −3.32, p = 0.556), nor admission rates (study 18.8%, control 17.8%, p = 0.131). We saw a decrease in opioid use (study 47.4%, control 60.0%, p < 0.01) and an increased use of non-opioid analgesics (study 27.3%, control 18.44%, p < 0.01).ConclusionsRemoving IV morphine in the ED, without a compensatory rise in alternative opioids, does not appear to significantly impact analgesia or disposition. These data favor a more limited opioid use strategy in the ED.     

Comparing Analgesia on an As-Needed Basis to Traditional Intravenous Patient-Controlled Analgesia Within Fast-Track Orthopedic Procedures: A Randomized Controlled Trial

BackgroundThe aim was to determine if the use of intravenous patient-controlled analgesia (IVPCA) in a fast-track joint replacement program is associated with increased use of perioperative opioid consumption and increased length of hospital stay.DesignA prospective, double-blind, randomized controlled trial.SettingsAcademic hospital.Participants/SubjectsA total of 80 patients aged 18-85 years, with body mass index (BMI) 18-40, undergoing elective total knee arthroplasty were recruited.MethodsPre-operatively, patients received gabapentin, celecoxib, and acetaminophen. Peri-operatively, patients received spinal anesthesia with morphine and fentanyl, and periarticular local anesthetic administration by the surgeon. Postoperatively, 80 patients were randomized by a computer-generated sequence into IVPCA group (group A, n = 40) and non-IVPCA group (group B, n = 40).ResultsThe primary outcome was 48-hour postoperative opioid consumption and length of hospital stay. Secondary outcomes included side effects of opioids, patient satisfaction, and pain scores. There was no significant difference within 48-hour postoperative opioid consumption (median 61.3 vs. 87.5, p = .181) and length of hospital stay (median 49.8 hours vs. 49.5 hours; p = .89) between the two groups. Also, there was no significant difference in patient satisfaction (median 5 in both groups), pain scores, and opioid-related side effects.ConclusionsIVPCA was associated with nonsignificant reduction in opioid exposure in elective total knee arthroplasty surgery within 48 hours. Neither group was superior in terms of length of hospital stay, opioid related side-effects, pain scores, and patient satisfaction.     

Inconsistencies in opioid equianalgesic ratios: clinical and research implications

Cancer pain is common, occurring in up to 60% of patients and opioid conversion may be required for effective pain management. Conversion from one opioid to another can be problematic due to differences in equianalgesic ratios found in established resources. This study explores the implications of using various published equianalgesic ratios when converting to a common opioid unit. This secondary analysis includes 105 advanced cancer patients who reported use of transdermal fentanyl, long-acting oxycodone, or oral methadone. Common clinically used equianalgesic ratios were identified and utilized to calculate a parenteral morphine equivalent for each of the selected agents. When the equianalgesic ratios were applied to each drug, there were substantial differences in the calculated morphine equivalent for transdermal fentanyl (2-fold difference) and methadone (100-fold difference). The calculated difference for oxycodone was lower, with a 1.5-fold difference. This study demonstrates large variability in opioid conversions based on the use of common equianalgesic ratios for transdermal fentanyl, long-acting oxycodone, and methadone. These findings have important clinical and research implications. First, this study substantiates the use of these ratios as only guidelines for treatment. Second, it supports the need for well-designed, rigorous studies to evaluate opioid conversions. Third, this study demonstrates the need for a standard reporting system of opioid equianalgesic ratios employed in clinical trials.