Heroin-related Deaths Research Articles

A quantitative LC-MS/MS method for investigation of polysubstance use involving heroin and cocaine

Concurrent use of heroin and cocaine (known as the “speedball”) prevails among substance use disorder populations, especially in opioid-dependent individuals, with severe consequences and a high fatality rate. Little is known about the patterns and correlations of the concurrent use of heroin and cocaine. It is vital to investigate such a polydrug use in both humans and animals to uncover concomitant toxicity and the cause of fatal overdose (death). In this study, we aimed to shed some light on the role of cocaine in the etiology of heroin-related deaths in the context of molecular pharmacokinetics (PK). For the purpose, a high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of heroin, cocaine, and their metabolites in whole blood was developed and fully validated in accordance with the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines. Then, this method was used to analyze heroin, cocaine, and their metabolites in blood from the rats intraperitoneally administered non-lethal 10 mg/kg heroin or 20 mg/kg cocaine alone, or their combination that is lethal with a proximal mortality of 33 %. The obtained results from the rats that experienced the lethal toxicity revealed that the concurrent use of heroin and cocaine significantly increased the risk of fatality from overdose. Heroin significantly slowed down the elimination of cocaine and its main metabolites in blood, while cocaine significantly enhanced heroin metabolism from 6-monoacetylmorphine (6-MAM) to morphine. Similar elimination half-lives for other heroin metabolites were observed. These findings are reported for the first time in this study, facilitating our understanding of the polysubstance metabolism and severe consequences produced by the polydrug use.

Differences in heroin overdose deaths in Australia by age, 2020-2022: Disease and estimated survival times

BackgroundThe age of people who use illicit opioids has increased, with a clinical picture of accelerated ageing. The study aimed to determine, stratified by age: 1. The circumstances and characteristics of heroin-related toxicity deaths in Australia, 2020–2022; 2. The toxicological profile and autopsy findings; 3. The proportion of cases in which blood 6-acetyl morphine (6AM) was detected, as a measure of survival time. MethodsRetrospective study of 610 cases of fatal heroin-related drug toxicity in Australia, 2020–2022. Cases were stratified as: <30 years, 30–39 years, 40–49 years, ≥50 years. ResultsCompared to the youngest group, those aged ≥50 years were more likely to have a history of chronic pain (12.4 v 3.3 %), to have their death attributed to combined drug toxicity/disease (20.1 v 3.3 %), and to have evidence of a sudden collapse (21.3 v 11.1 %). There were no differences in free morphine concentrations or glucuronide concentrations. Compared to the youngest group, however, the two older groups were significantly more likely to have 6AM present in blood, a proxy measure of a shorter survival time (52.0, 55.2 v 34.5 %). Compared to the youngest group, cases aged ≥50 years were more likely to be diagnosed with cardiomegaly (44.0 v 16.7 %), coronary artery disease (46.0 v 15.0 %), emphysema (35.0 v 5.1 %), hepatic steatosis (15.4 v 3.4 %), hepatic fibrosis (17.6 v 3.4 %), and cirrhosis (19.8 v 0.0 %). ConclusionsOlder cases of heroin overdose had more extensive heart, lung, and liver disease, and appeared more likely to have shorter survival times.

Heroin-Related Fatalities in Jeddah, Saudi Arabia, between 2008 and 2018

To date, epidemiological studies have not evaluated heroin-related deaths in the Middle East and North African regions, especially Saudi Arabia. All heroin-related postmortem cases reported at the Jeddah Poison Control Center (JPCC) over a 10-year period (21 January 2008 to 31 July 2018) were reviewed. In addition, liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) was utilized to determine the 6-monoacetylmorphine (6-MAM), 6-acetylcodeine (6-AC), morphine (MOR), and codeine contents in unhydrolyzed postmortem specimens. Ninety-seven heroin-related deaths were assessed in this study, and they represented 2% of the total postmortem cases at the JPCC (median age, 38; 98% male). In the blood, urine, vitreous humor, and bile samples, the median morphine concentrations were 280 ng/mL, 1400 ng/mL, 90 ng/mL, and 2200 ng/mL, respectively; 6-MAM was detected in 60%, 100%, 99%, and 59% of the samples, respectively; and 6-AC was detected in 24%, 68%, 50%, and 30% of the samples, respectively. The highest number of deaths (33% of total cases) was observed in the 21-30 age group. In addition, 61% of cases were classified as "rapid deaths," while 24% were classified as "delayed deaths." The majority (76%) of deaths were accidental; 7% were from suicide; 5% were from homicide; and 11% were undetermined. This is the first epidemiological study to investigate heroin-related fatalities in Saudi Arabia and the Middle East and North African region. The rate of heroin-related deaths in Jeddah remained stable but increased slightly at the end of the study period. Most patients were heroin-dependent abusers and from the middle-aged group. The availability of urine, vitreous humor, and bile specimens provided valuable information regarding the opioids that were administered and the survival time following heroin injection.

Post-Mortem Analysis of Heroin Biomarkers, Morphine and Codeine in Stomach Wall Tissue in Heroin-Related Deaths.

Toxicological analysis of some cases can be complicated by poor sample quality caused by decomposition. Although heroin-related deaths have been researched extensively, the interpretation of toxicology findings in these cases is challenging, especially in instances where blood samples are unavailable. Thus, it is important to develop analytical methods for different sample types. In this study. a method for the quantification of 6-monoacetylmorphine, 6-acetylcodeine, morphine, and codeine in postmortem stomach wall tissue using liquid chromatography coupled with tandem mass spectrometry was developed and validated. All calibration curves prepared with the stomach wall tissue were linear and ranged from 0.5–1000 ng/g with determination coefficients of >0.99 and a lower limit of quantification of 1.0 ng/g. The coefficients of variation for within-run precision and between-run precision were <9%. Matrix effects of stomach wall tissues and their extraction recoveries were investigated and ranged from −19% to +17% and 76% to 80%, respectively. Among the 16 analyzed heroin-related death cases, 6-monoacetylmorphine, 6-acetylcodeine, morphine, and codeine were detected in 75%, 31%, 100%, and 94% of all stomach wall tissues with median concentrations of 90 ng/g, 20 ng/g, 140 ng/g, and 30 ng/g, respectively. This study provides new data on the distribution of 6-monoacetylmorphine, 6-Acetylcodeine, morphine, and codeine in postmortem stomach wall tissue and suggests the usefulness of alternative matrices for investigating heroin-related fatalities when blood samples are unavailable. In addition, the prevalence of 6-monoacetylmorphine in the stomach wall tissue was higher than that in the liver and kidney tissues.

Toxicity of heroin laced with synthetic opioid β-U10 and etizolam

Illicit heroin can be substituted or adulterated with New Psychoactive Substances (NPS) including highly potent fentanyl-type substances or other opioid-like compounds to counteract low-purity supply. The addition of unknown NPS to the heroin supply poses an additional risk of overdose and death. In 2020, the Emerging Drug Network of Australia VIC (EDNAV) study was funded to monitor drug related harm in individuals attending emergency departments (ED) at major hospitals within Victoria. In September 2020, a previously unreported NPS, β-U10 (2-napthyl-U-47700), was detected in discarded drug paraphernalia samples collected during a pilot study of an early warning system for illicit drug use in Melbourne, Australia. Subsequently, blood samples of EDNAV project individuals with positive heroin detections were analysed for β-U10, in addition to NPS and traditional illicit drugs. After liquid-liquid extraction, blood samples underwent extensive toxicological analysis via targeted liquid-chromatography tandem mass spectrometry (LC-MS/MS) and untargeted screening via high-resolution quadrupole time-of-flight mass spectrometry (LC-QTOF). Confirmation of β-U10 concentrations were measured via LC-MS/MS using certified reference material. In total, seven cases were found to contain synthetic opioid β-U10. Six samples were collected in October 2020, with the remaining case detected more than a year later in December 2021. Measured β-U10 concentrations ranged from 0.01 to 22 ng/mL (median 3 ng/mL). All cases also contained methylamphetamine and etizolam. Morphine was detected in all cases along with 6-acetylmorphine in three of these cases. Other drugs included diphenhydramine, diazepam, doxylamine, gamma-hydroxybutyrate, MDMA, methadone, and mitragynine. The average age was 37 and ranged from 20 to 52 years of age. All individuals presented to ED with varying levels of sedation (Glascow Coma Scale 3–14, median 9) and recovered with supportive care (median stay 6.8 hours). Two cases showed a positive response to naloxone. The Poisons Severity Score for one case was 3, with 4 cases assessed as level 2. The pharmacological activity of β-U10 is largely unknown. β-U10 was first published by the Upjohn Company in the 1970's and is a structural analogue of the widely reported NPS U-47700, which has approximately seven times greater affinity to the μ-opioid receptor than morphine (Cheney. Journal of Medicinal Chemistry 1985;28:1853–1864). U-47700 has been utilised recreationally for its sedative properties in addition to positive effect on mood. The co-ingestion of other sedatives and respiratory depressants, including opioids and the NPS benzodiazepine etizolam in each of these reported cases precludes definitive conclusions regarding the clinical effect of β-U10. Additional studies that examined heroin supply at the time found the addition of β-U10 was associated with a decrease in heroin purity. The detection of β-U10 in one case 12 months following the previous detection may indicate the drug re-supply of the adulterated mixture in Australia. The detection of β-U10 has also informed toxicological investigations into heroin-related deaths that occurred during the same time-period. The consumption of adulterated illicit substances by unsuspecting individuals with unknown compounds such as β-U10, particularly in conjunction with other opioids and CNS depressants such as etizolam, is an alarming trend and poses a significant public health risk.

The systematic investigation of the role of adulterants into the postmortem redistribution of heroin

We aimed to investigate systematically the impact of adulterants on postmortem in vivo pharmacokinetic of heroin and its metabolites by determining the postmortem redistribution (PMR) of heroin in this study. Heroin (1 mg/kg) was administered intravenously to the rats. The rats were euthanized 1 hour after drug administrations, followed by placed in the supine position at room temperature. Femoral (right and left), subclavian, cardiac blood samples and liver, lung, kidney, myocardium and brain samples were collected at the time of death, postmortem 1st, 4th and 24th hour. Heroin (1 mg/kg) containing adulterants (1 mg/kg paracetamol, dextromethorphan and caffeine) was administered intravenously to the same number of rat groups, and the same procedures were repeated. All blood and organ tissue samples were analysed with validated liquid-liquid extraction methods using a liquid chromatography tandem-mass spectrometer. The changes in the levels of heroin metabolites during the postmortem interval were determined in different blood and tissue samples included in our study. Accordingly, apart from the minimal statistical differences in morphine concentrations in the left femoral blood, significant differences in each matrix throughout the postmortem interval, especially in heart blood, lung and kidney tissue were observed. In contrast to morphine, there are minimal differences in morphine-3-glucurinide concentrations in heart tissue and other matrices. Graphical differences were observed between morphine concentrations in heart blood, liver, myocardium and lung of animal groups in the presence of adulterants and animal groups in which heroin was administered alone. The findings obtained in this study may play an important role in elucidating heroin-related death cases by forensic toxicologists or pathologists.

6-Monoacetylmorphine-antibody distribution in tissues from heroin-related death cases: An experimental study to investigate the distributive response.

Heroin, a semisynthetic opioid drug synthesized from morphine, is the 3,6‐diacetyl ester of morphine (diacetylmorphine). The post‐mortem diagnosis of heroin‐related death could be an issue and usually rely on a combination of investigations, including the autopsy, histological and toxicological analysis. We conducted the present study to evaluate the correlation between the heroin concentration in biological fluids (peripheral blood, bile and urine) and the post‐mortem anti‐6‐MAM antibody expression in various tissues (brain, heart, lung, liver and kidney) using immunohistochemical staining. A quantitative analysis of the immunohistochemical reaction was carried out. 45 cases of heroin‐related death investigated at the Forensic Pathology Institutes of the University of Rome, Foggia and Pisa were included. The control group was composed of 15 cases of death due to other causes, without brain lesions and negative toxicological analysis for drugs. We found a positive immunohistochemical reaction in different organs and it was related to the timing of heroin metabolization. No reaction was found in the control group. Our findings show that immunohistochemistry can be a valuable tool for the post‐mortem diagnosis of acute heroin abuse. A better understanding of the timing of heroin's metabolism can be useful in the forensic field and for future therapeutic applications.

Histological paraffin-embedded block: a good alternative specimen to detect the use of opiates at least 20 years ago

PurposeSince the solely certain remnants of a performed autopsy are formalin-fixed paraffin-embedded (FFPE) samples, stored in the archives of every institute of legal medicine, we managed to extract molecules of toxicological interest from these specimens.MethodsWe assessed the analysis of ten fresh liver samples collected from heroin-related deaths and then histologically processed the same samples. The embedded blocks were then extracted by means of a new extracting method and the eluates were measured. We also selected five toxicological cases of heroin-related fatalities that were examined 20 years ago, collected the toxicological result documents of the analysis that were carried out at the time and then processed the corresponding FFPE liver samples that were stored in the archives.ResultsWe managed to isolate heroine-related metabolites from 20-year-old paraffin-embedded blocks and calculated ratios to evaluate the performance of our new extraction.ConclusionsAccording to our study, it is feasible to carry out a toxicological examination on old histological samples and, therefore, this matrix can be considered as a new alternative specimen for chemical-analytical evaluations of past cases or when fresh samples are not available anymore. The new extractive method was evaluated as efficient in treating these complex, paraffin-embedded samples. It was surprising that the target compounds could be quantitated from FFPE bocks created as long as 20 years ago.

Opioid related deaths in Norway in 2000–2019

AimsThe aim of the study is to present autopsy-based findings of the most prevalent opioids in overdose deaths in Norway from 2000 to 2019, as such data are lacking in the current literature. MethodsData on cause of death obtained from the Norwegian Cause of Death Registry (NCoDR) were linked with forensic toxicological results from forensic autopsies. ResultsFrom year 2000 the annual numbers of overdose deaths decreased, specifically during 2000–2003, thereafter a relatively stable annual number was observed. Opioids were detected in 93% of the cases. Heroin related deaths have decreased, whereas medical opioids for pain treatment have increased with time. Men in their early 40′s dominate the overall numbers of deaths, but significantly different sex patterns emerge when studying the specific drugs. During the past 20 years, the mean age at overdose death has increased by 10 years (from 33 to 43 years). Overdose deaths without any illicit drugs present at autopsy have increased in recent years. These deaths, where only potentially prescription medications were detected, were more common among women and with higher age. ConclusionsIn Norway during the past 20 years, we observe a dynamic shift in overdose deaths caused by heroin and illicit drugs, to include a gradually increasing trend of overdose deaths from pill based pain medications and also methadone and buprenorphine. This warrants a shift in preventive responses, as the target groups differ.

The Public Health Approach to the Worsening Opioid Crisis in the United States Calls for Harm Reduction Strategies to Mitigate the Harm From Opioid Addiction and Overdose Deaths

The opioid crisis has devastated the U.S. more than any other country, and the epidemic is getting worse. While opioid prescriptions have decreased by more than 40% from its peak in 2010, unfortunately, opioid-related overdose deaths have not declined but continued to increase. With greater scrutiny on prescription opioids, many users switched to the cheaper and more readily available heroin that drove up heroin-related overdose deaths from 2010 to peak in 2016, being overtaken by the spike in synthetic opioid (mostly fentanyl)-related overdose deaths. The surge in fentanyl-related overdose deaths since 2013 is alarming as fentanyl is more potent and deadly. One thing is certain the opioid crisis is not improving but has become dire with the surge in fentanyl-related overdose deaths. Evidence-based strategies have to be implemented in the U.S. to control this epidemic before it destroys more lives. Other countries, including European countries and Canada, have invested more in harm reduction strategies than the U.S. even though they (especially Europe) do not face anywhere near the level of crisis as the U.S. In the long-run, upstream measures (tackling the social determinants of health) are more effective public health strategies to control the epidemic. In the meantime, however, harm reduction strategies have to be employed to mitigate the harm from addiction and overdose deaths.

Enhanced heroin self-administration and distinct dopamine adaptations in female rats.

Increasing evidence suggests that females are more vulnerable to the harmful effects of drugs of abuse, including opioids. Additionally, rates of heroin-related deaths substantially increased in females from 1999 to 2017 [1], underscoring the need to evaluate sex differences in heroin vulnerability. Moreover, the neurobiological substrates underlying sexually dimorphic responding to heroin are not fully defined. Thus, we evaluated male and female Long Evans rats on acquisition, dose-responsiveness, and seeking for heroin self-administration (SA) as well as using a long access model to assess escalation of intake at low and high doses of heroin, 0.025 and 0.1 mg/kg/inf, respectively. We paired this with ex vivo fast-scan cyclic voltammetry (FSCV) in the medial nucleus accumbens (NAc) shell and quantification of mu-opioid receptor (MOR) protein in the ventral tegmental area (VTA) and NAc. While males and females had similar heroin SA acquisition rates, females displayed increased responding and intake across doses, seeking for heroin, and escalation on long access. However, we found that males and females had similar expression levels of MORs in the VTA and NAc, regardless of heroin exposure. FSCV results revealed that heroin exposure did not change single-pulse elicited dopamine release, but caused an increase in dopamine transporter activity in both males and females compared to their naïve counterparts. Phasic-like stimulations elicited robust increases in dopamine release in heroin-exposed females compared to heroin-naïve females, with no differences seen in males. Together, our results suggest that differential adaptations of dopamine terminals may underlie the increased heroin SA behaviors seen in females.

Longitudinal Opioid Surveillance Project Involving Toxicologic Analysis of Postmortem Specimens from 9 Counties in Michigan Suggests the Discovery of New High-Intensity Drug Trafficking Areas.

Acetyl fentanyl (AF) is a Schedule I fentanyl analog that has been increasingly seen in heroin and fentanyl polydrug toxicity overdoses in Michigan (MI). Drug users are often unaware of the presence of AF in their drugs because it is often sold mixed into or disguised as heroin. High levels of AF in heroin drug products can cause increased incidence of overdose. This article describes data from a longitudinal opioid surveillance program and details 102 decedents in MI who were found to have evidence of heroin in their postmortem blood. A large portion of these decedents were also found to have evidence of fentanyl and AF. Our data further show significant overlap in incidence rates of AF and heroin-related overdose deaths in several MI counties, suggesting that AF is becoming enmeshed in heroin trafficking. Furthermore, we report unprecedented high incidence rates of AF and heroin-related overdose deaths in Calhoun county, and we propose that it is a high-intensity drug trafficking area. Highways US-131 and US-31 are likely used to transport these drugs. More study is needed into the drug trafficking trends in MI to ascertain drug sources and monitor the ever developing and dangerous polydrug heroin combinations.

Correlation study between anatomopathological data and levels of blood morphine concentrations in heroin-related deaths.

Heroin-related mortality is a complex phenomenon involving several factors that make an individual more susceptible to opioid toxicity. Among these, pre-existing pathological conditions play an important role. The current paper reviewed 51 autopsied cases performed over the last 30years, each subject ("frequent heroin user") having taken heroin intravenously alone before death. For each case, total blood morphine concentration determined by gas chromatography-mass spectrometry (GC-MS) was obtained from the archives. For histopathological evaluation we examined microscopic sections of the heart, lung, brain, liver and kidney, and for each organ a score table with a numerical value from 1 to 5, as an indicator of increasing severity, was drawn up. Finally, we created a scoring system based on the Injury Severity Score (ISS), generated by the sum of the squares of the three highest organ scores. We investigated the relationship between total blood morphine value (mg/l) and pathological score by inserting the two variables in a linear regression model: Score=a+b·Morphinemia (p-value <0.001). The results demonstrated a statistically significant correlation between the two variables: individuals with low total blood morphine values tended to have a higher pathological score. Our study provides useful assessment tools for forensic practice, confirming the need to combine two important disciplines in drug death investigation: forensic pathology and toxicology.

Do prescription drug monitoring programs encourage prescription – or illicit – opioid abuse?

Background Prescription drug monitoring programs (PDMPs) are tools that states can use to fight prescription opioid misuse within their jurisdiction. However, because PDMPs make prescription opioids more difficult to access, these programs may have the unintended consequence of increasing deaths related to illicit opioids. Methods: This study uses fixed effects models to estimate how PDMP regulatory strength is associated with both prescription opioid- and heroin-related deaths between 1999 and 2016. PDMP regulatory strength is measured by creating a score using multiple correspondence analysis (MCA). Additional models replace the MCA score with a binary indicator for the presence of one particular regulation requiring physicians to access the system before writing opioid prescriptions. Results: Results show that continuous measures of PDMP strength are not generally associated with prescription opioid- or heroin-related death rates. Yet, one model does show that PDMP scores are positively associated with the heroin-related death rate. The models using the binary mandatory access variable show a strong positive association with both prescription opioid and heroin deaths. Conclusions: This study supports the theory that more stringent state PDMPs are associated with higher rates of heroin-related deaths, potentially due to decreases in prescription opioid availability.

Postmortem Liver and Kidney Tissue Concentrations of Heroin Biomarkers and Their Metabolites in Heroin‐Related Fatalities*†

A method was developed and validated for analyzing 6-monoacetylmorphine, morphine, 6-acetylcodeine, and codeine in routine postmortem liver and kidney specimens using liquid chromatography-tandem mass spectrometry. Samples were prepared with a Stomacher instrument followed by solid-phase extraction. All calibration curves [0.5-1000ng/g] were linear with coefficients of determination greater than 0.99 and limits of quantification of 1.0ng/g. Within-run precision ranged between 2.0% and 8.0%, between-run precision ranged between 1.0% and 9.0%, and accuracy ranged between -5.0% and +3.0%. Matrix effects ranged from -18% to +9%. After matrix effects were excluded, analytical recoveries ranged from 76% to 94%. The distributions of 6-monoacetylmorphine, morphine, 6-acetylcodeine, and codeine were investigated in 31 postmortem cases in which heroin was the primary cause of death. In the current study, the median free morphine ratios were calculated for liver to blood and kidney to blood, which were 2.2 and 4.0, respectively. The current report highlights the importance of testing multiple specimens, including liver and kidney, in heroin-related deaths, especially if no blood samples are available. Furthermore, this work presents new information regarding the distribution of heroin metabolites in liver and kidney.

The impact of the abuse-deterrent reformulation of extended-release OxyContin on prescription pain reliever misuse and heroin initiation

The introduction of abuse-deterrent OxyContin in 2010 was intended to reduce its misuse by making it more tamper resistant. However, some studies have suggested that this reformulation might have had unintended consequences, such as increases in heroin-related deaths. We used the 2005–2014 cross-sectional U.S. National Survey on Drug Use and Health to explore the impact of this reformulation on intermediate outcomes that precede heroin-related deaths for individuals with a history of OxyContin misuse. Our study sample consisted of adults who misused any prescription pain reliever prior to the reformulation of OxyContin (n = 81,400). Those who misused OxyContin prior to the reformulation were considered the exposed group and those who misused other prescription pain relievers prior to the reformulation were considered the unexposed group. We employed multivariate logistic regression under a difference-in-differences framework to examine the effect of the reformulation on five dichotomous outcomes: prescription pain reliever misuse; prescription pain reliever use disorder; heroin use; heroin use disorder; and heroin initiation. We found a net reduction in the odds of prescription pain reliever misuse (OR:0.791, p < 0.001) and heroin initiation (OR:0.422, p = 0.011) after the reformulation for the exposed group relative to the unexposed group. We found no statistically significant effects of the reformulation on prescription pain reliever use disorder (OR: 0.934, p = 0.524), heroin use (OR: 1.014p = 0.941), and heroin use disorder (OR: 1.063, p = 0.804). Thus, the reformulation of OxyContin appears to have reduced prescription pain reliever misuse without contributing to relatively greater new heroin use among those who misused OxyContin prior to the reformulation.

Mortalities of methamphetamine, opioid, and ketamine abusers in Shanghai and Wuhan, China

Studies on the mortalities of drug abusers in China are scarce. This study explores the deaths of methamphetamine, opioid, and ketamine abusers in Shanghai (2004–2017) and Wuhan (2005–2017). Chi-square/Fisher’s exact tests were used to compare the differences in terms of region, gender, age, cause of death, and the method used in the last drug abuse. Poisson regression models were used to estimate the rate ratios (“RRs”) and annual percentage changes (“APCs”). 314 heroin, 43 methamphetamine, and 4 ketamine abusers were included. Furthermore, simultaneously, 6 abusers used heroin and methamphetamine, and 7 abusers used methamphetamine and ketamine. Heroin-related deaths have declined in Shanghai (APC, −16.1; 95 % CI, −18.4 to −11.3) and Wuhan (APC, −16.0; 95 % CI, −18.9 to −10.6), whereas methamphetamine-related deaths have increased in Wuhan (APC, 12.8; 95 % CI, 0.0 to 29.2). On the whole, in the two cities, males were more frequently observed than females in heroin-related deaths (4.4, 230/52). However, the gender ratios for methamphetamine- (1.8, 34/19) and ketamine-related deaths (1.2, 6/5) were close to one. In view of the mortality rates of the drug abusers in most Chinese cities were still unclear, it is thus important to improve mortality surveillance of the drug abusers at the national level.

783. Infectious complications in IV abusers: a detailed review of hospitalized IV abusers

BackgroundWith 337 heroin-related deaths between 2009 and 2013, Suffolk County reported more such deaths than any other county in New York State. Suffolk County’s population of 1.5 million is larger than that of some states. Compared with the rest of New York State, median annual household income is the third highest of New York’s 62 counties and the income gap between socioeconomic classes is smaller.MethodsDetailed retrospective chart review was performed on admitted patients to Stony Brook University Hospital (SBUH) from November 2015 to October 2018 with active IV drug abuse and infection. Demographics, drug use characteristics, microbiology, co-morbidities, and outcome were assessed.Results198 active IV heroin users were admitted with a complicated infection during this time frame. Most patients were Caucasian (94%) and more were male (64%). The median age was 33 (range 17 to 58). Most patients (90%) had health insurance, many lived with others at home and were unemployed. Thirty-three were on methadone and 28 on suboxone. The median length of stay was 4.7 days (ranging from 1 to 140 days) and 29% of admitted patients left against medical advice. 60% of the patients had been admitted to a hospital in the prior 12 months. The majority (58%) presented with cellulitis, 12% were diagnosed with endocarditis, 10% with osteomyelitis, 6.5% with bacteremia/sepsis. Ten were also pregnant. Infectious disease was consulted in 55%, and Psychiatry and social worker in 46% of cases. HIV, HepC and HBV testing were not performed in less than 50% of patients. There was a total of 5 deaths during the hospitalization, 2 patients with endocarditis, 2 with sepsis and one overdose. 45% of patients with endocarditis and 43% of patients with osteomyelitis required surgical intervention. S. aureus was a common pathogen and identified in 61% of the cases, where a pathogen was isolated.ConclusionOur data show that even in an affluent community opioid addiction is not properly addressed during hospital admissions. As a consequence, users sign out against medical advice, have frequent hospital admissions, remain out of addiction treatment, and outcome is poor. A systematic multidisciplinary approach will be required to improve the care for this vulnerable patient populationDisclosures All authors: No reported disclosures.

Postmortem Fluid Concentrations of Heroin Biomarkers and Their Metabolites.

Only limited data exist concerning the utility of complementary specimens in heroin-related deaths. As such, this report employed a validated LC-MS-MS method to quantify 6-monoacetylmorphine (6-MAM), 6-acetylcodeine (6-AC), and their metabolites morphine and codeine in blood with (BN) and without preservative (B) and the additional unpreserved specimens of vitreous humor, urine, stomach contents, and bile from 20 postmortem cases in which heroin was the primary cause of death. The median concentration of 6-MAM in BN was 0.011mg/L, B was 0.008mg/L, urine was 0.186mg/L, vitreous humor was 0.022mg/L, stomach contents was 0.147mg/L, and bile was 0.012mg/L. Only one case was found to be positive for 6-AC in B (case 6, 0.002mg/L), and the median concentration of 6-AC was 0.002mg/L in BN, 0.012mg/L in urine, 0.003mg/L in vitreous humor, 0.057mg/L in stomach contents, and 0.004mg/L in bile. These findings present new information on the distribution of these analytes in complementary matrices and support their inclusion for accurately determining the role of heroin in opioid-related deaths.

Separation and Detection of Trace Fentanyl from Complex Mixtures Using Gradient Elution Moving Boundary Electrophoresis

The current opioid epidemic remains an ongoing challenge, exacerbated by the extreme potency of synthetic opioids (e.g., fentanyl and fentanyl analogues), leading to an increase in adulterated heroin-related deaths. The increasing prevalence of fentanyl and fentanyl analogues in mixtures with heroin and other adulterants, excipients, and bulking agents has placed an emphasis on trace analysis methods for their detection from complex drug mixtures. Here, gradient elution moving boundary electrophoresis (GEMBE), a robust and miniaturized electrophoretic separation technique, was employed for the separation and detection of fentanyl and nine (9) fentanyl analogues from mixtures. GEMBE incorporated a short capillary (5 cm × 15 μm i.d.) for the electrophoretic separation of analytes with an opposing bulk counterflow. As the velocity of the counterflow was varied, analytes with differing electrophoretic mobilities entered the separation channel at different times and were analyzed as moving boundaries by contactless conductivity detection. The continuous injection of sample, driven by a controlled and variable pressure, both provided selectivity of the analytes and prevented contaminants or particulate within the sample from entering the separation capillary. Fentanyl was successfully separated and detected down to 2.5 μmol/L and demonstrated only 50% to 60% signal suppression in dilute binary mixtures with heroin and other common adulterants and excipients at 30:1 (compound/fentanyl) concentration ratios. In addition, GEMBE was successfully applied to a few adjudicated case samples of fentanyl-related mixtures exhibiting dyes and visible particulate. The short capillaries, contactless detection format utilized here, and continuous injection of sample allow for a small footprint platform that is easy-to-use for forensic analyses.