Refractory Hypoglycemia Due to Sulfonylurea Contamination of Illicit Opioid Medications.

Illicit drug supply adulteration can heighten the risk for adverse health outcomes. Sulfonylurea medications are widely used in the treatment of diabetes mellitus (DM). Unintentional or intentional overdose of sulfonylureas can cause refractory hypoglycemia. This case report describes a 62-year-old male patient who presented to the emergency department (ED) after being found on the ground with signs of mild trauma. He was noted to be persistently hypoglycemic despite boluses of intravenous dextrose, a dextrose infusion, and oral nutrition. The patient did report purchase and oral ingestion of pills sold as oxycodone and that the pill shape and color were different from his usual supply. The patient was empirically treated with octreotide resulting in normalization of his serum glucose. Testing demonstrated a serum glipizide concentration six times the reporting range. This case represents unintentional sulfonylurea exposure in the setting of non-prescribed oxycodone use, resulting in hypoglycemia refractory to intravenous dextrose and oral nutrition. Octreotide is an additional potential treatment for this condition. As in this case, ingestion of street drugs may present a potential source of sulfonylurea exposure. Opioid contamination with sulfonylureas has not been widely reported in the literature and knowledge about this potential exposure is important for the prompt recognition and treatment of these patients by emergency physicians.

State-level variation in distribution of oxycodone and opioid-related deaths from 2000 to 2021: an ecological study of ARCOS and CDC WONDER data in the USA.

OBJECTIVES: This study aims to characterise oxycodone's distribution and opioid-related overdoses in the USA by state from 2000 to 2021. DESIGN: This is an observational study. SETTING: More than 80 000 Americans died of an opioid overdose in 2021 as the USA continues to struggle with an opioid crisis. Prescription opioids play a substantial role, introducing patients to opioids and providing a supply of drugs that can be redirected to those seeking to misuse them. METHODS: The Drug Enforcement Administration annual summary reports from the Automation of Reports and Consolidated Orders System provided weights of oxycodone distributed per state by business type (pharmacies, hospitals and practitioners). Weights were converted to morphine milligram equivalents (MME) per capita and normalised for population. The Centers for Disease Control and Prevention Wide-ranging ONline Data for Epidemiologic Research provided mortality data for heroin, other opioids, methadone, other synthetic narcotics and other/unspecified narcotics. RESULTS: There was a sharp 280.13% increase in total MME/person of oxycodone from 2000 to 2010, followed by a slower 54.34% decrease from 2010 to 2021. Florida (2007-2011), Delaware (2003-2020) and Tennessee (2012-2021) displayed consistent and substantial elevations in combined MME/person compared with other states. In the peak year (2010), there was a 15-fold difference between the highest and lowest states. MME/person from only pharmacies, which constituted >94% of the total, showed similar results. Hospitals in Alaska (2000-2001, 2008, 2010-2021), Colorado (2008-2021) and DC (2000-2011) distributed substantially more MME/person over many years compared with other states. Florida stood out in practitioner-distributed oxycodone, with an elevation of almost 15-fold the average state from 2006 to 2010. Opioid-related deaths increased +806% from 2000 to 2021, largely driven by heroin, other opioids and other synthetic narcotics. CONCLUSIONS: Oxycodone distribution across the USA showed marked differences between states and business types over time. Investigation of opioid policies in states of interest may provide insight for future actions to mitigate opioid misuse.

Trends in hydrocodone combination product exposures reported to California Poison Control System (CPCS) following DEA rescheduling.

CONTEXT: On October 6, 2014, the United States Drug Enforcement Administration (DEA) implemented a regulatory change for hydrocodone combination products (HCPs), moving them from Schedule III to II, in an effort to decrease drug overdoses. Existing research suggests this regulatory action reduced HCP prescribing and dispensing; however, there is limited research assessing its possible effects on overdoses and accidental exposures. OBJECTIVE: To analyze the changes in opioid exposures reported to the California Poison Control System (CPCS) before and after DEA rescheduling of HCPs. METHODS: We collected monthly exposure data reported to CPCS from 2012 to 2019 and conducted interrupted time series analyses to assess changes in exposures after rescheduling for HCPs, tramadol, oxycodone, morphine, codeine, fentanyl, and heroin. Additional analyses were done to assess any changes in exposures resulting in severe outcomes (moderate or major health effects). For HCPs, we also conducted logistic regressions to identify characteristics of exposures resulting in severe outcomes before and after rescheduling. RESULTS: Overall monthly opioid exposures reported to CPCS decreased after DEA rescheduling of HCPs. These decreases were significant for HCP, tramadol, and morphine (p < 0.001). Exposures significantly increased for heroin and fentanyl (p < 0.001). There were no significant changes in the share of severe outcomes attributed to HCP exposures after rescheduling. DISCUSSION: The DEA rescheduling of HCPs was associated with a significant decrease in HCP exposures and prescription opioid exposures overall, but was associated with increased fentanyl and heroin exposures. While other initiatives may have contributed to this decrease, our findings suggest that rescheduling may be a useful regulatory strategy to reduce drug exposures. CONCLUSION: DEA rescheduling of HCPs was associated with a significant reduction in prescription opioid exposures, suggesting that rescheduling high-risk drugs may be an effective strategy to improve public health.

Diffuse subcortical white matter injury and bilateral basal ganglia neuronal loss after acute opioid overdose.

Opiate intoxication has been associated with life-threatening effects of sympathetic suppression and respiratory depression, but current literature is limited in describing its neurotoxic effects on the central nervous system. Here, we present the case of an otherwise high-functioning adolescent male who was found unresponsive after ingestion of approximately 3-4 fake oxycodone 10-325 mg pills laced with fentanyl. Magnetic resonance imaging showed evidence of diffuse T2 hyperintensities in the corpus callosum and bilateral frontal, parietal, and cerebellum indicative of diffuse white matter injury. In addition, there were distinct areas of restricted diffusion in the bilateral basal ganglia concerning for oxidative stress-mediated neuronal loss. His neurological exam improved with supportive treatment over the course of his hospitalization. Although limited literature has shown leukoencephalopathy to be associated with opioid overdose, we present a case of additional involvement of subcortical gray matter.

Accidental Overdose Deaths in Oklahoma, 2002-2017: Opioid and Methamphetamine Trends.

To evaluate trends related to accidental overdose deaths in Oklahoma, with a focus on opioids and methamphetamine. All accidental drug overdose deaths in the state of Oklahoma from 2002 to 2017 were reviewed. Opioids were grouped into the following categories: all opioids, prescription opioids, synthetic opioids and heroin. Age-adjusted death rates for methamphetamine and each opioid category were calculated and analyzed. Accidental overdoses accounted for 9,936 deaths during the study period. Of these, opioids were seen in 62.9%, with prescription opioids comprising 53.8%, synthetic opioids 10.3% and heroin 2.8%. Synthetic opioids, despite a recent upward nationwide trend, showed a slight overall decrease (-6.8%) from 2009 to 2017. In contrast, methamphetamine showed a 402.2% increase from 2009 to 2017 and an overall increase of 1,526.7%. Methamphetamine was involved in the most overdoses (1,963), followed by oxycodone (1,724). Opioid-related deaths were most common among white individuals (90.3%) and showed a slight male predilection (56.9%). With the intent of assessing the opioid epidemic as it relates to accidental overdoses in Oklahoma, this study suggests that opioid-related overdoses have slowed in recent years amidst a sharp increase in methamphetamine deaths.

Prescription Opioid Prescribing in Western Europe and the United States.

Pain is universal, yet the prevalence of overdose and treatment of pain varies significantly between the United States (US) and Western Europe. Overdose deaths are seven times more common in the US compared to Western Europe. Cultural perceptions of pain, perception and treatment of opioid use disorder, pharmaceutical advertising, and rates and regulation of prescribing of opioids represent examples of factors that may be related to such differences between the US and Western Europe. As Rhode Island continues to battle the devastating and well-documented national opioid overdose epidemic, we should consider how cultural, regulatory differences, and economic factors may influence pain and its treatment.

The impact of the prescription opioid epidemic on young children: Trends and mortality.

BACKGROUND: Our objective was to describe trends and deaths in young children associated with opioid analgesics. METHODS: Analysis of pediatric exposures using the RADARS System Poison Center Program from July 1, 2010 through December 31, 2018. Cases involving a child < 6 years, with an exposure to one or more opioids: buprenorphine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, oxymorphone, and tramadol. Poisson regression was used to model the shape of the time response curve. RESULTS: 48,560 cases were identified, median age 2 years (IQR 1.4, 2.0), 52.4 % male. The most commonly involved opioid was hydrocodone (32.5 %); buprenorphine and methadone had the highest exposure rates when adjusted for dispensed prescriptions (0.84 and 0.73 per 10,000 prescriptions). There were 28 deaths, methadone being the most commonly involved opioid (16). Exposures decreased significantly accounting for population (from 8.39 to 4.19 exposures per 100,000 children) and per prescription (from 0.33 to 0.25 exposures per 10,000 prescriptions). After adjustment for prescriptions, the exposure rate for hydromorphone and fentanyl increased over the study period, while buprenorphine had the greatest decrease in exposure rate. Among 28 deaths, 11 (39 %) were known or suspected to have been exposed, but medical care was not sought or was delayed. CONCLUSION: Pediatric opioid exposure rates by prescription and population decreased from July 2010 through December 2018. However, with over 48,000 exposures and 28 deaths, the opioid epidemic continues to impact young children. Many exposures including deaths were preventable. Continued improvements in prevention require a multifaceted approach.

Elevated Lipase in an Infant with Altered Mental Status.

The pancreatic enzymes lipase and amylase serve important functions in digestion/absorption of fats and polysaccharides. Measurement of these enzymes is often used in the emergency department to rule out acute pancreatitis in patients with nonspecific abdominal pain. In acute pancreatitis, serial measurements of plasma lipase and amylase typically follow a predictable temporal pattern of rise-and-fall kinetics: lipase levels rise within 4 to 8 hours, crest at 2× to 50× the upper reference limit at 24 hours, and decline to normal concentrations in 7 to 14 days. In situations in which the duration and magnitude of pancreatic enzyme elevation are more transient, clinicians should consider alternative causes for enzyme elevation. In this case report, incidental discovery of elevated lipase in an African American baby girl who ingested oxycodone resulted in additional laboratory and radiological work-up. Stronger awareness of exogenous influences on gastrointestinal motility may have prevented the need for further testing in this patient.

Comparing rates and characteristics of ambulance attendances related to extramedical use of pharmaceutical opioids in Victoria, Australia from 2013 to 2018.

BACKGROUND AND AIMS: Despite increases in opioid prescribing and related morbidity and mortality, few studies have comprehensively documented harms across opioid types. We examined a population-wide indicator of extramedical pharmaceutical opioid-related harm to determine if the supply-adjusted rates of ambulance presentations, the severity of presentations or other attendance characteristics differed by opioid type. DESIGN: Retrospective observational study of coded ambulance patient care records related to extramedical pharmaceutical opioid use, January 2013 to September 2018. SETTING: Australia CASES: Primary analyses used Victorian data (n = 9823), with available data from other Australian jurisdictions (n = 4338) used to determine generalizability. MEASUREMENTS: We calculated supply-adjusted rates of attendances using Poisson regression, and used multinomial logistic regression to compare demographic, presentation severity, mental health, substance use and other characteristics of attendances associated with seven pharmaceutical opioids. FINDINGS: In Victoria, the highest rates of attendance [per 100 000 oral morphine equivalent mg (OME)] were for codeine (0.273/100 000) and oxycodone (0.113/100 000). The lowest rates were for fentanyl (0.019/100 000) and tapentadol (0.005/100 000). Oxycodone-naloxone rates (0.031/100 000) were lower than for oxycodone as a single ingredient (0.113/100 000). Fentanyl-related attendances were associated with the most severe characteristics, most likely to be an accidental overdose, most likely to have naloxone administered and least likely to be transferred to hospital. In contrast, codeine-related attendances were more likely to involve suicidal thoughts/behaviours, younger females and be transported to hospital. Supply-adjusted attendance rates for individual opioids were stable over time. Victorian states were broadly consistent with non-Victorian states. CONCLUSIONS: In Australia, rates and characteristics of opioid-related harm vary by opioid type. Supply-adjusted ambulance attendance rates appear to be both stable over time and unaffected by large changes in supply.

Associations Between Opioid Prescribing Patterns and Overdose Among Privately Insured Adolescents.

OBJECTIVES: Little is known about the risk for overdose after opioid prescription. We assessed associations between the type of opioid, quantity dispensed, daily dose, and risk for overdose among adolescents who were previously opioid naive. METHODS: Retrospective analysis of 1 146 412 privately insured adolescents ages 11 to 17 years in the United States captured in the Truven MarketScan commercial claims data set from January 2007 to September 2015. Opioid overdose was defined as any emergency department visit, inpatient hospitalization, or outpatient health care visit during which opioid overdose was diagnosed. RESULTS: Among our cohort, 725 participants (0.06%) experienced an opioid overdose, and the overall rate of overdose events was 28 events per 100 000 observed patient-years. Receiving ≥30 opioid tablets was associated with a 35% increased risk for overdose compared to receiving ≤18 tablets (hazard ratio [HR] = 1.35; 95% confidence interval: 1.05-1.73; P = .02). Daily prescribed opioid dose was not independently associated with an increased risk for overdose. Tramadol exposure was associated with a 2.67-fold increased risk for opioid overdose compared to receiving oxycodone (adjusted HR = 2.67; 95% confidence interval: 1.90-3.75; P < .0001). Adolescents with preexisting mental health conditions demonstrated increased risk for overdose, with HRs ranging from 1.65 (anxiety) to 3.09 (substance use disorders). CONCLUSIONS: One of 1600 (0.06%) previously opioid-naive adolescents who received a prescription for opioids experienced an opioid overdose a median of 1.75 years later that resulted in medical care. Preexisting mental health conditions, use of tramadol, and higher number of dispensed tablets (>30 vs <18) were associated with an increased risk of opioid overdose.

Opioid Deaths in Milwaukee County, Wisconsin 2013-2017: The Primacy of Heroin and Fentanyl.

Heroin and fentanyl are the overwhelming and increasing cause of opioid deaths in Milwaukee County, Wisconsin. We reviewed all drug and opioid deaths from 2013 to 2017 to delineate the specific opioid drugs involved and changes in their incidence. From 2013 to 2017, 980 deaths were due to opioids, rising from 184 in 2013 to 337 in 2017. In 2017, opioid deaths exceeded combined non-natural deaths from homicide and suicide. Illicit heroin and fentanyl/analogs caused 84% of opioid deaths and 80% of drug deaths, with no increase in deaths due to oral prescription drugs such as oxycodone and hydrocodone. Any approach to decreasing this dramatic increase in opioid deaths should first focus on interdicting the supply and cheap availability of these illicit opioids. Fentanyl and its analogs represent the most deadly opioids and the greatest threat to human life in our population.

Comparative out-of-hospital mortality of long-acting opioids prescribed for non-cancer pain: A retrospective cohort study.

PURPOSE: Despite significant growth of opioid prescriptions, only limited data are available regarding the comparative safety of long-acting opioids for chronic non-cancer pain. Recent data suggest that transdermal fentanyl and oxycodone CR may have greater toxicity than morphine SR in patients with non-cancer pain. Thus, we compared the risk of out-of-hospital deaths in patients with non-cancer pain filling prescriptions for transdermal fentanyl or oxycodone CR with that for morphine SR. METHODS: We conducted a retrospective cohort study in 50 658 patients enrolled in Tennessee Medicaid who filled prescriptions for transdermal fentanyl (n = 8717), oxycodone CR (n = 14 118), or morphine SR (n = 27 823) between 1999 and 2011. We excluded individuals with cancer or other life-threatening diagnoses and used propensity scores to adjust for multiple potential confounders. The primary outcome was out-of-hospital mortality. RESULTS: During 44 385 person-years of follow-up, 689 patients died. The out-of-hospital mortality rate among all study subjects was 155/10 000 patient-years. Contrary to earlier data suggesting greater risk, mortality was not significantly different in patients filling prescriptions for transdermal fentanyl compared with morphine SR (adjusted HR = 0.96, 95% C.I.: 0.77-1.21); moreover, patients filling prescriptions for oxycodone CR had lower mortality risk compared with those filling prescriptions for morphine SR (adjusted HR = 0.79, 95% C.I. 0.66-0.95). CONCLUSION: In the study population, long-acting opioids for non-cancer pain were associated with high out-of-hospital mortality rates. We found comparable out-of-hospital mortality risks associated with transdermal fentanyl and morphine SR. The risk of out-of-hospital death for oxycodone CR was lower than that for morphine SR.

At-a-glance - The role of opioid toxicity in suicide deaths in Alberta, 2000 to 2016. / Aperçu - Suicides et intoxication aux opioïdes en Alberta (2000-2016).

Given the current opioid crisis in Canada, there is interest in the role of opioid toxicity in suicide deaths, particularly in whether any observed patterns are similar to those of unintentional deaths. The present analysis examined characteristics of opioid-toxicity suicide, and its role in relation to other suicide methods, from 2000 to 2016 in Alberta. It does not appear that the opioid crisis has resulted in a disproportionately higher number of suicides in Alberta. Individuals who die from unintentional opioid toxicity and those who die by opioid-toxicity suicide are likely distinct populations, requiring nuanced public health responses for prevention.

RÉSUMÉ: Dans le cadre de la crise actuelle des opioïdes au Canada, il est important de s'intéresser au rôle joué par l'intoxication aux opioïdes dans les décès par suicide et, plus particulièrement, de déterminer si les tendances observées à cet égard sont similaires aux tendances observées pour les décès accidentels. Dans cette analyse, on examine les caractéristiques du suicide par intoxication aux opioïdes et la corrélation entre cette méthode et d'autres moyens de suicide entre 2000 et 2016 en Alberta. La crise des opioïdes ne semble pas avoir causé un nombre disproportionnellement élevé de suicides en Alberta. Les personnes qui décèdent des suites d'une intoxication accidentelle aux opioïdes et celles qui se suicident en s'intoxiquant avec des opioïdes constituent probablement des populations différentes, ce qui nécessite des interventions préventives nuancées en matière de santé publique.

Correlations between population-levels of prescription opioid dispensing and related deaths in Ontario (Canada), 2005-2016.

Canada is experiencing an ongoing opioid-related public health crisis, including persistently rising opioid (e.g., poisoning) mortality. Previous research has documented marked correlations between population-levels of opioid dispensing and deaths. We examined possible correlations between annual population-level dispensing of specific opioid formulations and related poisoning deaths in Ontario (Canada), for the period 2005-2016. Annual coroner statistics-based numbers of poisoning deaths associated with six main opioid formulations (codeine, fentanyl, hydromorphone, methadone, morphine, and oxycodone) for Ontario were converted into annual death rates (per 100,000 population). Annual dispensing data for the opioid formulations under study were based on commercial retail-sales data from a representative, stratified sample of community pharmacies (IMSQuintiles/IQVIA CompuScript), converted into Defined Daily Doses (DDD/1,000 population/day). Possible relationships between the annual death and dispensing rates were assessed by Pearson's correlation coefficient analyses. Death rates increased for almost all, while dispensing rates increased for half of the opioid categories. A significant positive correlation between death and dispensing rates was found for hydromorphone (r = 0.97, 95% CI: 0.88-0.99) and oxycodone (r = 0.90, 95% CI: 0.68-0.97) formulations; a significant negative correlation was found for codeine (r = -0.78, 95% CI: -0.93 to -0.37). No significant correlations were detected for fentanyl, methadone, and morphine related deaths. Strong correlations between levels of dispensing and deaths for select opioid formulations were found. For select others, extrinsic factors - e.g., increasing involvement of non-medical opioid products (e.g., fentanyl) in overdose deaths - likely confounded underlying correlation effects. Opioid dispensing levels continue to influence population-level mortality levels, and need to be addressed by prevention strategies.

Conditional power for assessing population interventions.

AIM: To calculate conditional power in comparative two-period studies with previously observed baseline data. METHOD: Isolate the variability attributable to the yet-to-observed data and modify the standard power formulae. RESULTS: For illustration, we examine rates of opioid overdose before and after a reformulation of one opioid product. The null hypothesis posited no impact of the reformulation, alternative hypotheses posited possible impacts, and ancillary hypotheses posited different secular pre-post changes directly observable in comparators. Conditional power varied with the size of the comparator population and with the assumed pre-post change for the comparator. CONCLUSION: Pre-post designs can be initiated after the baseline period is over. Power calculations that are conditioned on observed baseline data account differently for variability in the baseline and follow-up periods.

Opioid drug poisonings in Ohio adolescents and young adults, 2002-2014.

CONTEXT: Opioids represent a drug class that adolescents and young adults intentionally misuse and abuse. When taken on their own or with other substances in this manner, opioids pose an increased risk of overdose and potential death. OBJECTIVE: To determine trends of opioid drug poisonings among adolescents and young adults in Ohio from 2002 to 2014 using Poison Control Center (PCC) data. METHODS: Data were obtained from Ohio PCCs from 2002 to 2014 for opioid drug poisonings amongst 10-29 year olds. Trends were evaluated with Poisson regression. Ohio counties with higher opioid drug poisoning rates were identified using age-adjusted resident population estimates. Chi-square tests were conducted to compare these county rates to the Ohio rate. RESULTS: Both unintentional and intentional Ohio PCC opioid drug poisonings peaked in 2009, and there were significant declines through 2014. Almost 40% of intentional opioid drug poisonings were for young adults aged 18-24 years. Suspected suicide poisonings were 64.9% female, misuse poisonings were 54.5% male, and abuse poisonings were 60.1% male. Commonly reported substances included tramadol, heroin, and acetaminophen combinations with hydrocodone or oxycodone. Benzodiazepines and ethanol were the most common substances reported in conjunction with opioids. The top four Ohio counties with significantly higher opioid drug poisoning rates than the state average in 2014 were Hamilton, Mahoning, Butler, and Fairfield. CONCLUSION: This study enhances the understanding of Ohio's opioid epidemic so that future prevention efforts and legislation can better target needed resources. Both males and females would benefit from opioid education early in their lives.

The curse of relieving pain.

A 39-year-old woman with a history of chronic back pain due to spinal haemangiomas, multiple malignancies and depression was brought by Emergency medical servicesS to the emergency centre (EC) after being found unresponsive on the bathroom floor. The patient had an exacerbation of her back pain the previous day for which she admitted to taking double her usual dose of oxycodone, in addition to alprazolam, lorazepam, diphenhydramine and a glass of wine. She reported that she lost consciousness and was down for over 8 hours. In the EC, she complained of right forearm pain which was accompanied by mild diffuse soft-tissue swelling and decreased sensation in the right hand. Radial pulse was intact. Creatine kinase was found to be at 4663 U/L. The patient was found to have acute compartment syndrome and underwent emergent forearm fasciotomy. She eventually regained full function of the right arm.

Risk factors for severe respiratory depression from prescription opioid overdose.

BACKGROUND AND AIMS: Prescription opioid overdose is a leading cause of injury-related morbidity and mortality in the United States. We aimed to identify characteristics associated with clinical severity in emergency department patients with prescription opioid overdose. DESIGN: This was a secondary data analysis of adult prescription opioid overdoses from a large prospective cohort of acute overdoses. We examined elements of a typical emergency department evaluation using a multivariable model to determine which characteristics were associated with clinical severity, specifically severe respiratory depression (SRD). SETTING: This study was conducted at two urban academic emergency departments in New York City, USA. PARTICIPANTS: Adult patients who presented with acute prescription opioid overdose between 2009 and 2013 were included in the current study. We analyzed 307 patients (mean age = 44.7, 42% female, 2.0% mortality). MEASUREMENTS: Patient demographics, reported substances ingested, suspected intent for ingesting the substance, vital signs, laboratory data, treatments including antidotes and intubation and outcome of death were recorded by trained research assistants. Intent was categorized into four mutually exclusive categories: suicide, misuse, therapeutic error and undetermined. The primary outcome was SRD, defined as administration of either (a) naloxone or (b) endotracheal intubation (ETI). FINDINGS: A total of 109 patients suffered SRD with 90 patients receiving naloxone alone, nine ETI alone and 10 both naloxone and ETI. The most common opioids were oxycodone (n = 124) and methadone (n = 116). Mean age was higher in patients with SRD (51.1 versus 41.1, P < 0.001). Opioid misuse was associated with SRD in the multivariable analysis [odds ratio (OR) = 2.07, 95% confidence interval (CI) = 1.21-3.55]. The unadjusted relative risk of SRD was high for fentanyl (83.3% SRD) and lowest for codeine (3.6% SRD). CONCLUSION: In emergency department patients in the United States with prescription opioid overdose, worse clinical severity was associated with opioid misuse, increased with age and was widely variable, depending on the specific opioid medication involved.