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Pain Physician May 2016Opioid overdose continues to be a significant and growing cause of preventable mortality and morbidity. Studies suggest that unintentional, non-fatal overdose from... (Review)
Review
BACKGROUND
Opioid overdose continues to be a significant and growing cause of preventable mortality and morbidity. Studies suggest that unintentional, non-fatal overdose from prescription opioid analgesics constitutes a large portion of total overdose events. The societal burden associated with these events is a frequently overlooked public health concern.
OBJECTIVES
To evaluate unintentional, non-fatal prescription opioid overdoses, including the identification of risk factors, societal burden, and knowledge gaps where further study is warranted.
STUDY DESIGN
Systematic review of the literature for unintentional, non-fatal opioid overdose.
METHODS
Preferred reporting items for systematic reviews and meta-analyses guidelines were used in constructing this systematic review. To determine the scope of the existing literature, a systematic search was conducted using the MEDLINE, CINAHL, PsycINFO, and Web of Science databases.
RESULTS
This systematic review analyzes 24 articles (21 retrospective descriptive analyses, 2 prospective analyses, one phase III trial, and one meta-analysis). Articles were reviewed by authors and relevant data examined. Results show that opioid overdose morbidity is significantly more prevalent than mortality and sequelae of non-fatal events should be studied in more detail.
LIMITATIONS
The limitations of this systematic review include the range of study populations and opioids discussed and the broad and variable definitions of "opioid overdose" in the literature.
CONCLUSIONS
Opioid overdose morbidity and mortality is seen across the entire spectrum of inpatient and outpatient use with significant numbers of adverse events occurring in population segments not identified by high risk indicators. Increased physician awareness and a multi-modal approach could help mitigate the overdose epidemic while maintaining effective pain control for patients.
KEY WORDS
Prescription, opioid, accidental drug overdose, unintentional overdose, drug poisoning, fentanyl, oxycodone, hydrocodone, methadone, oxymorphone, hydromorphone.
Topics: Analgesics, Opioid; Drug Overdose; Humans; Prescription Drug Overuse
PubMed: 27228510
DOI: No ID Found -
JAMAIs oxycodone associated with greater efficacy and fewer adverse events compared with alternative analgesics for cancer pain?
CLINICAL QUESTION
Is oxycodone associated with greater efficacy and fewer adverse events compared with alternative analgesics for cancer pain?
BOTTOM LINE
Oxycodone was not associated with superior cancer pain relief or fewer adverse effects compared with other strong opioids, such as morphine or oxymorphone. However, the quality of the evidence was low.
Topics: Analgesics, Opioid; Humans; Neoplasms; Oxycodone; Pain; Pain Management
PubMed: 26393852
DOI: 10.1001/jama.2015.8556 -
Journal of Forensic Sciences Jul 2015Effects of benzodiazepines on postmortem opioid parent and parent/metabolite blood concentration ratios were determined for fentanyl-, hydrocodone-, methadone-, or...
Effects of benzodiazepines on postmortem opioid parent and parent/metabolite blood concentration ratios were determined for fentanyl-, hydrocodone-, methadone-, or oxycodone-related accidental deaths. These opioids are partially metabolized by the CYP3A4 enzyme system, which is also affected by diazepam and alprazolam. Opioid/metabolite combinations examined were as follows: fentanyl/norfentanyl, hydrocodone/dihydrocodeine, methadone/EDDP, and oxycodone/oxymorphone. Parent opioid concentrations were analyzed for 877 deaths. Parent/metabolite concentration ratios were analyzed for 349 deaths, excluding cases with co-intoxicants present known to interfere with opioid elimination. Alprazolam in combination with diazepam significantly decreased median hydrocodone concentrations by 48% (p = 0.01) compared to hydrocodone alone. The methadone parent/metabolite concentration ratio was reduced by 35% in the presence of diazepam compared to methadone alone (p = 0.03). Benzodiazepines did not statistically significantly affect fentanyl or oxycodone concentrations. Possible factors affecting opioid concentrations and possible toxicity development, including any differential effects on specific opioids, should continue to be explored.
Topics: Accidents; Adult; Aged; Analgesics, Opioid; Benzodiazepines; Databases, Factual; Drug Overdose; Female; Forensic Toxicology; Humans; Male; Middle Aged; Opioid-Related Disorders; West Virginia; Young Adult
PubMed: 26223761
DOI: 10.1111/1556-4029.12807 -
Journal of Pain Research 2015To evaluate the conversion of opioid-experienced patients with chronic moderate-to-severe pain to extended-release morphine sulfate with sequestered naltrexone...
A multicenter, primary-care-based, open-label study to assess the success of converting opioid-experienced patients with chronic moderate-to-severe pain to morphine sulfate and naltrexone hydrochloride extended-release capsules using a standardized conversion guide.
OBJECTIVE
To evaluate the conversion of opioid-experienced patients with chronic moderate-to-severe pain to extended-release morphine sulfate with sequestered naltrexone hydrochloride (MSN) using a standardized conversion guide.
METHODS
This open-label, single-arm study was conducted in 157 primary care centers in the United States. A total of 684 opioid-experienced adults with chronic moderate-to-severe pain were converted to oral administration of MSN from transdermal fentanyl and oral formulations of hydrocodone, hydromorphone, methadone, oxycodone, oxymorphone, and other morphine products using a standardized conversion guide. The primary endpoint was the percentage of patients achieving a stable MSN dose within a 6-week titration phase. Secondary endpoints included duration of time to stable dose, number of titration steps, safety and efficacy measures, and investigator assessment of conversion guide utility.
RESULTS
Of the 684 patients, 51.3% were converted to a stable dose of MSN (95% confidence interval: 47.5%, 55.1%). The mean (standard deviation) number of days to stable dose was 20 (8.94), and number of titration steps to stable dose was 2.4 (1.37). The majority of adverse events were mild/moderate and consistent with opioid therapy. Mean pain scores at stable dose decreased from baseline. Investigators were generally satisfied with the conversion guide and, in 94% of cases, reported they would use it again.
CONCLUSION
Conversion to MSN treatment using the standardized MSN conversion guide was an attainable goal in approximately half of the population of opioid-experienced patients with chronic moderate-to-severe pain. Investigators found the guide to be a useful tool to assist conversion of opioid-experienced patients to MSN.
PubMed: 26185466
DOI: 10.2147/JPR.S82395 -
American Journal of Veterinary Research Jul 2015To establish the minimum alveolar concentration (MAC) of desflurane and evaluate the effects of 2 opioids on MAC in sheep. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To establish the minimum alveolar concentration (MAC) of desflurane and evaluate the effects of 2 opioids on MAC in sheep.
ANIMALS
8 adult nulliparous mixed-breed sheep.
PROCEDURES
A randomized crossover design was used. Each sheep was evaluated individually on 2 occasions (to allow assessment of the effects of each of 2 opioids), separated by a minimum of 10 days. On each occasion, sheep were anesthetized with desflurane in 100% oxygen, MAC of desflurane was determined, oxymorphone (0.05 mg/kg) or hydromorphone (0.10 mg/kg) was administered IV, and MAC was redetermined. Physiologic variables and arterial blood gas and electrolyte concentrations were measured at baseline (before MAC determination, with end-tidal desflurane concentration maintained at 10%) and each time MAC was determined. Timing of various stages of anesthesia was recorded for both occasions.
RESULTS
Mean ± SEM MAC of desflurane was 8.6 ± 0.2%. Oxymorphone or hydromorphone administration resulted in significantly lower MAC (7.6 ± 0.4% and 7.9 ± 0.2%, respectively). Cardiac output at MAC determination for desflurane alone and for desflurane with opioid administration was higher than that at baseline. No difference was identified among hematologic values at any point. Effects of oxymorphone and hydromorphone on durations of various stages of anesthesia did not differ significantly.
CONCLUSIONS AND CLINICAL RELEVANCE
MAC of desflurane in nulliparous adult sheep was established. Intravenous administration of oxymorphone or hydromorphone led to a decrease in MAC; however, the clinical importance of that decrease was minor relative to the effect in other species.
Topics: Adjuvants, Anesthesia; Analgesics, Opioid; Anesthetics, Inhalation; Animals; Blood Gas Analysis; Cardiac Output; Cross-Over Studies; Desflurane; Female; Hydromorphone; Infusions, Intravenous; Isoflurane; Oxymorphone; Pulmonary Alveoli; Sheep
PubMed: 26111087
DOI: 10.2460/ajvr.76.7.583 -
The Cochrane Database of Systematic... May 2015Agitation is a common experience for people living with dementia, particularly as day-to-day function and cognition start to decline more. At the present time there are... (Review)
Review
BACKGROUND
Agitation is a common experience for people living with dementia, particularly as day-to-day function and cognition start to decline more. At the present time there are limited pharmacological options for relieving agitation and little is known about the safety and efficacy of opioid drugs in this setting.
OBJECTIVES
To determine the clinical efficacy and safety of opioids for agitation in people with dementia.
SEARCH METHODS
We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group Specialized Register, on 13 June 2014 using the terms: narcotic OR opioid OR opium OR morphine OR buprenorphine OR codeine OR dextromoramide OR diphenoxylate OR dipipanone OR dextropropoxyphene OR propoxyphene OR diamorphine OR dihydrocodeine OR alfentanil OR fentanyl OR remifentanil OR meptazinol OR methadone OR nalbuphine OR oxycodone OR papaveretum OR pentazocine OR meperidine OR pethidine OR phenazocine OR hydrocodone OR hydromorphone OR levorphanol OR oxymorphone OR butorphanol OR dezocine OR sufentanil OR ketobemidone.ALOIS contains records of clinical trials identified from monthly searches of a number of major healthcare databases such as MEDLINE, EMBASE and PscyINFO, as well as numerous trial registries and grey literature sources.
SELECTION CRITERIA
Randomised, controlled trials of opioids compared to placebo for agitation in people with dementia.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed the studies identified by the search against the inclusion criteria.
MAIN RESULTS
There are currently no completed randomised, placebo controlled trials of opioids for agitation in dementia. There are two potentially relevant trials still in progress.
AUTHORS' CONCLUSIONS
We found insufficient evidence to establish the clinical efficacy and safety of opioids for agitation in people with dementia. There remains a lack of data to determine if or when opioids either relieve or exacerbate agitation. More evidence is needed to guide the effective, appropriate and safe use of opioids in dementia.
Topics: Analgesics, Opioid; Dementia; Humans; Psychomotor Agitation
PubMed: 25972091
DOI: 10.1002/14651858.CD009705.pub2 -
MMWR. Morbidity and Mortality Weekly... May 2015On January 23, 2015, the Indiana State Department of Health (ISDH) began an ongoing investigation of an outbreak of human immunodeficiency virus (HIV) infection, after...
On January 23, 2015, the Indiana State Department of Health (ISDH) began an ongoing investigation of an outbreak of human immunodeficiency virus (HIV) infection, after Indiana disease intervention specialists reported 11 confirmed HIV cases traced to a rural county in southeastern Indiana. Historically, fewer than five cases of HIV infection have been reported annually in this county. The majority of cases were in residents of the same community and were linked to syringe-sharing partners injecting the prescription opioid oxymorphone (a powerful oral semi-synthetic opioid analgesic). As of April 21, ISDH had diagnosed HIV infection in 135 persons (129 with confirmed HIV infection and six with preliminarily positive results from rapid HIV testing that were pending confirmatory testing) in a community of 4,200 persons.
Topics: Adolescent; Adult; Causality; Coinfection; Comorbidity; Disease Outbreaks; Female; HIV Infections; Hepatitis C; Heroin; Humans; Indiana; Male; Methenamine; Middle Aged; Oxymorphone; Pregnancy; Pregnancy Complications, Infectious; Rural Population; Sexual Partners; Substance Abuse, Intravenous; Young Adult
PubMed: 25928470
DOI: No ID Found -
Journal of Clinical Laboratory Analysis May 2016Oxycodone is a widely used opioid for pain management and patient's compliance with therapy is often monitored by using oxycodone immunoassay. The performance of the DRI... (Comparative Study)
Comparative Study
Comparison of Response of DRI Oxycodone Semiquantitative Immunoassay With True Oxycodone Values Determined by Liquid Chromatography Combined With Tandem Mass Spectrometry: Sensitivity of the DRI Assay at 100 ng/ml Cut-Off and Validity of Semiquantitative Value.
OBJECTIVE
Oxycodone is a widely used opioid for pain management and patient's compliance with therapy is often monitored by using oxycodone immunoassay. The performance of the DRI oxycodone immunoassay was compared with liquid chromatography combined with tandem mass spectrometry (LC/MS/MS) assay.
MATERIALS AND METHODS
In 48 urine specimens collected from patients taking oxycodone, urinary oxycodone concentrations were determined using LC/MS/MS and the DRI oxycodone immunoassay for application on the Cobas c 501 analyzer (Roche Diagnostics, Indianapolis, IN).
RESULTS
Out of 48 specimens, 14 specimens showed oxycodone value less than 100 ng/ml, seven specimens had low positive values (between 101 and 165 ng/ml) and all other specimens had values 165 to 1789 ng/ml using the LC/MS/MS assay. The DRI oxycodone assay successfully identified all oxycodone specimens with oxycodone concentrations over the 100 ng/ml. In addition, the DRI assay also showed positive response in 11 out of 14 specimens with oxycodone values less than 100 ng/ml. However, semiquantitative values obtained by the DRI assay did not match with true oxycodone and metabolite oxymorphone concentrations combined obtained by using LC/MS/MS.
CONCLUSIONS
DRI oxycodone immunoassay at 100 ng/ml is a reliable immunoassay for analysis of oxycodone in urine.
Topics: Chromatography, Liquid; Humans; Immunoassay; Ions; Oxycodone; Reference Standards; Reproducibility of Results; Sensitivity and Specificity; Tandem Mass Spectrometry
PubMed: 25715994
DOI: 10.1002/jcla.21834 -
CPT: Pharmacometrics & Systems... Dec 2014Evaluation of a potential risk of metabolic drug-drug interactions (DDI) is of high importance in the clinical setting. In this study, a physiologically based...
Evaluation of a potential risk of metabolic drug-drug interactions (DDI) is of high importance in the clinical setting. In this study, a physiologically based pharmacokinetic (PBPK) model was developed for oxycodone and its two primary metabolites, oxymorphone and noroxycodone, in order to assess different DDI scenarios using published in vitro and in vivo data. Once developed and refined, the model was able to simulate pharmacokinetics of the three compounds and the DDI extent in case of coadministration with an inhibitor, as well as the oxymorphone concentration variation between CYP2D6 extensive metabolizers (EM) and poor metabolizers (PM). The reliability of the model was tested against published clinical studies monitoring different inhibitors and dose regimens, and all predicted area under the concentration-time curve (AUC) ratios were within the twofold acceptance range. This approach represents a strategy to evaluate the impact of coadministration of different CYP inhibitors using mechanistic incorporation of drug-dependent and system-dependent available in vitro and in vivo data.
PubMed: 25518025
DOI: 10.1038/psp.2014.49 -
The Cochrane Database of Systematic... Sep 2014Osteoarthritis is the most common form of joint disease and the leading cause of pain and physical disability in older people. Opioids may be a viable treatment option... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Osteoarthritis is the most common form of joint disease and the leading cause of pain and physical disability in older people. Opioids may be a viable treatment option if people have severe pain or if other analgesics are contraindicated. However, the evidence about their effectiveness and safety is contradictory. This is an update of a Cochrane review first published in 2009.
OBJECTIVES
To determine the effects on pain, function, safety, and addiction of oral or transdermal opioids compared with placebo or no intervention in people with knee or hip osteoarthritis.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and CINAHL (up to 28 July 2008, with an update performed on 15 August 2012), checked conference proceedings, reference lists, and contacted authors.
SELECTION CRITERIA
We included randomised or quasi-randomised controlled trials that compared oral or transdermal opioids with placebo or no treatment in people with knee or hip osteoarthritis. We excluded studies of tramadol. We applied no language restrictions.
DATA COLLECTION AND ANALYSIS
We extracted data in duplicate. We calculated standardised mean differences (SMDs) and 95% confidence intervals (CI) for pain and function, and risk ratios for safety outcomes. We combined trials using an inverse-variance random-effects meta-analysis.
MAIN RESULTS
We identified 12 additional trials and included 22 trials with 8275 participants in this update. Oral oxycodone was studied in 10 trials, transdermal buprenorphine and oral tapentadol in four, oral codeine in three, oral morphine and oral oxymorphone in two, and transdermal fentanyl and oral hydromorphone in one trial each. All trials were described as double-blind, but the risk of bias for other domains was unclear in several trials due to incomplete reporting. Opioids were more beneficial in pain reduction than control interventions (SMD -0.28, 95% CI -0.35 to -0.20), which corresponds to a difference in pain scores of 0.7 cm on a 10-cm visual analogue scale (VAS) between opioids and placebo. This corresponds to a difference in improvement of 12% (95% CI 9% to 15%) between opioids (41% mean improvement from baseline) and placebo (29% mean improvement from baseline), which translates into a number needed to treat (NNTB) to cause one additional treatment response on pain of 10 (95% CI 8 to 14). Improvement of function was larger in opioid-treated participants compared with control groups (SMD -0.26, 95% CI -0.35 to -0.17), which corresponds to a difference in function scores of 0.6 units between opioids and placebo on a standardised Western Ontario and McMaster Universities Arthritis Index (WOMAC) disability scale ranging from 0 to 10. This corresponds to a difference in improvement of 11% (95% CI 7% to 14%) between opioids (32% mean improvement from baseline) and placebo (21% mean improvement from baseline), which translates into an NNTB to cause one additional treatment response on function of 11 (95% CI 7 to 14). We did not find substantial differences in effects according to type of opioid, analgesic potency, route of administration, daily dose, methodological quality of trials, and type of funding. Trials with treatment durations of four weeks or less showed larger pain relief than trials with longer treatment duration (P value for interaction = 0.001) and there was evidence for funnel plot asymmetry (P value = 0.054 for pain and P value = 0.011 for function). Adverse events were more frequent in participants receiving opioids compared with control. The pooled risk ratio was 1.49 (95% CI 1.35 to 1.63) for any adverse event (9 trials; 22% of participants in opioid and 15% of participants in control treatment experienced side effects), 3.76 (95% CI 2.93 to 4.82) for drop-outs due to adverse events (19 trials; 6.4% of participants in opioid and 1.7% of participants in control treatment dropped out due to adverse events), and 3.35 (95% CI 0.83 to 13.56) for serious adverse events (2 trials; 1.3% of participants in opioid and 0.4% of participants in control treatment experienced serious adverse events). Withdrawal symptoms occurred more often in opioid compared with control treatment (odds ratio (OR) 2.76, 95% CI 2.02 to 3.77; 3 trials; 2.4% of participants in opioid and 0.9% of participants control treatment experienced withdrawal symptoms).
AUTHORS' CONCLUSIONS
The small mean benefit of non-tramadol opioids are contrasted by significant increases in the risk of adverse events. For the pain outcome in particular, observed effects were of questionable clinical relevance since the 95% CI did not include the minimal clinically important difference of 0.37 SMDs, which corresponds to 0.9 cm on a 10-cm VAS.
Topics: Administration, Cutaneous; Administration, Oral; Analgesics, Opioid; Humans; Osteoarthritis, Hip; Osteoarthritis, Knee; Pain Measurement; Randomized Controlled Trials as Topic
PubMed: 25229835
DOI: 10.1002/14651858.CD003115.pub4