A Series of 8 Illicit Fentanyl Intoxication Deaths in Infants and Toddlers.

ABSTRACT: We report 8 children younger than 2 years who died from acute illicit fentanyl intoxications in Connecticut between 2020 and 2022.The Connecticut Office of the Chief Medical Examiner (CT OCME) investigates all unexpected, violent, and suspicious deaths in Connecticut. The CT OCME's electronic database was searched for fentanyl deaths by age. All underwent autopsies and toxicology testing.The ages ranged from 28 days to 2 years (mean age, 12 months). The causes of death involved acute fentanyl intoxications with 1 having xylazine, 1 having para-fluorofentanyl, and 1 having cocaine and morphine. All the manners of death were certified as homicide. The postmortem fentanyl blood concentrations ranged from 0.40 to 46 ng/mL. Most of the children were found unresponsive after being put to sleep. Three were co-sleeping with adults (2 in bed; 1 on a recliner). There was a known history of parental/caregiver drug abuse in 7 of 8 of the fatalities.We summarize the key investigative, autopsy, and toxicological findings. As illicit fentanyl use increases, there is a potential for infant exposure and death. The investigation and certification of these deaths and the role of intentional administration versus inadvertent exposure due to caregiver neglect in the context of the certification of the manner of death are described.

Causes of death among people who used illicit opioids in England, 2001-18: a matched cohort study.

BACKGROUND: In many countries, the average age of people who use illicit opioids, such as heroin, is increasing. This has been suggested to be a reason for increasing numbers of opioid-related deaths seen in surveillance data. We aimed to describe causes of death among people who use illicit opioids in England, how causes of death have changed over time, and how they change with age. METHODS: In this matched cohort study, we studied patients in the Clinical Practice Research Datalink with recorded illicit opioid use (defined as aged 18-64 years, with prescriptions or clinical observations that indicate use of illicit opioids) in England between Jan 1, 2001, and Oct 30, 2018. We also included a comparison group, matched (1:3) for age, sex, and general practice with no records of illicit opioid use before cohort entry. Dates and causes of death were obtained from the UK Office for National Statistics. The cohort exit date was the earliest of date of death or Oct 30, 2018. We described rates of death and calculated cause-specific standardised mortality ratios. We used Poisson regression to estimate associations between age, calendar year, and cause-specific death. FINDINGS: We collected data for 106 789 participants with a history of illicit opioid use, with a median follow-up of 8·7 years (IQR 4·3-13·5), and 320 367 matched controls with a median follow-up of 9·5 years (5·0-14·4). 13 209 (12·4%) of 106 789 participants in the exposed cohort had died, with a standardised mortality ratio of 7·72 (95% CI 7·47-7·97). The most common causes of death were drug poisoning (4375 [33·1%] of 13 209), liver disease (1272 [9·6%]), chronic obstructive pulmonary disease (COPD; 681 [5·2%]), and suicide (645 [4·9%]). Participants with a history of illicit opioid use had higher mortality rates than the comparison group for all causes of death analysed, with highest standardised mortality ratios being seen for viral hepatitis (103·5 [95% CI 61·7-242·6]), HIV (16·7 [9·5-34·9]), and COPD (14·8 [12·6-17·6]). In the exposed cohort, at age 20 years, the rate of fatal drug poisonings was 271 (95% CI 230-313) per 100 000 person-years, accounting for 59·9% of deaths at this age, whereas the mortality rate due to non-communicable diseases was 31 (16-45) per 100 000 person-years, accounting for 6·8% of deaths at this age. Deaths due to non-communicable diseases increased more rapidly with age (1155 [95% CI 880-1431] deaths per 100 000 person-years at age 50 years; accounting for 52·0% of deaths at this age) than did deaths due to drug poisoning (507 (95% CI 452-562) per 100 000 person-years at age 50 years; accounting for 22·8% of deaths at this age). Mirroring national surveillance data, the rate of fatal drug poisonings in the exposed cohort increased from 345 (95% CI 299-391) deaths per 100 000 person-years in 2010-12 to 534 (468-600) per 100 000 person-years in 2016-18; an increase of 55%, a trend that was not explained by ageing of participants. INTERPRETATION: People who use illicit opioids have excess risk of death across all major causes of death we analysed. Our findings suggest that population ageing is unlikely to explain the increasing number of fatal drug poisonings seen in surveillance data, but is associated with many more deaths due to non-communicable diseases. FUNDING: National Institute for Health Research.

Troponin, A Predictor of Mortality in Methadone Exposure: An Observational Prospective Study.

Background Methadone poisoning/overdose is a global public health problem. We aimed to determine whether methadone poisoning increased cardiac troponin and whether high-sensitivity cardiac troponin I (hs-cTnI) levels predicted the need for intensive care unit admission, intubation, and mortality. Methods and Results This observational, prospective single-center study was done at Loghman-Hakim Hospital (Tehran, Iran) from June 2018 until February 2019. Patients aged >14 years admitted with a diagnosis of methadone exposure were included. Patients were excluded if they had coexisting conditions associated with elevated hs-cTnI levels. An ECG and hs-cTnI levels were obtained on emergency department presentation. Patients were followed up on their need for intubation, intensive care unit admission, and in-hospital mortality. Of 245 included patients (186 [75.9%] men; median age, 33 years), most referred to loss of consciousness (210 cases, 89%). Nineteen (7.7%) patients had hs-cTnI levels of >0.1 ng/mL (positive), and 41 (16.7%) had borderline levels of 0.019 to 0.1 ng/mL. Twenty-three (9.3%) cases were admitted to the intensive care unit, 21 (8.5%) needed intubation, and 5 (2%) died during hospitalization. An hs-cTnI cutoff value of 0.019 ng/mL independently predicted mortality. For optimal concomitant sensitivity and specificity, receiver operating characteristic curve analysis was conducted and showed that hs-cTnI had an independent significant association with mortality, with a cutoff value of 0.0365 ng/mL (odds ratio, 38.1; 95% CI, 2.3-641.9; P<0.001). Conclusions Methadone exposure/toxicity is a newly identified cause of elevated hs-cTnI. Values >0.019 ng/mL, and particularly >0.0365 ng/mL, of hs-cTnI predicted mortality in our sample. Future studies should measure troponin levels in methadone maintenance treatment clients to assess the risk of myocardial injury from long-term exposure.

Methadone-related deaths among youth and young adults in Sweden 2006-15.

AIMS: To identify methadone-related deaths and determine the prevalence among youth and young adults in Sweden 2006-15. DESIGN, SETTING AND PARTICIPANTS: National retrospective registry study comparing data from all forensic autopsy examinations and toxicology cases involving methadone during 2006-15 in individuals aged 15-29 years with police records, previous pharmaceutical prescriptions and health-care episodes. MEASUREMENTS: Multinomial logistic regression. To assess the factors contributing to the deaths, we compared individuals with and without previous substance use treatment and opioid use-related diagnoses with regard to previous opioid agonist treatment (OAT), psychiatric care and previous pain medication. To assess the circumstances of deaths, we analyzed the presence of other drugs and other factors at time of death. FINDINGS: We identified 269 methadone-related deaths, and the rate increased during the study period. Seventy-two (27%) cases had not previously received substance use treatment, 112 (42%) had received treatment but had no opioid use-related diagnosis and 85 (32%) had received treatment and had an opioid use-related diagnosis. In total, only 10 individuals had been prescribed methadone during the year before death. Prescriptions of benzodiazepines (60%), antidepressants (62%) and opioids for pain (22%) the year before death were common. Most deaths occurred during sleep with a time lag from ingestion of methadone. CONCLUSION: Prescription opioid- and methadone-related deaths increased in the group aged 15-29 years in Sweden between 2006 and 2015. Exposure to non-prescribed methadone and prescribed benzodiazepines, antidepressants and opioids for pain appears to be common in drug-related deaths in youth and young adults in Sweden.

"Chasing the Dragon": A Fatal Case Report of Toxic Leucoencéphalopathie Due to Inhaled Heroin.

BACKGROUND: Leukoencephalopathy is a myelin disorder caused by multiple agents, including substance abuse. CASE: A 28-year-old man arrived at the emergency department having suffered from asthenia, dizziness, disorientation and ataxia for two months. He had a two-year history of heroin inhalation. He arrived in a normal physical condition. Brain magnetic resonance showed bilateral diffuse hypointense lesions in the white matter. At day 3 after admission, he presented neurological deterioration, stupor, haemodynamic instability, respiratory failure, and died. DISCUSSION: Toxic leukoencephalopathy symptoms start with inattention, memory and personality changes, and may eventually cause dementia and death. Heroin inhalation is a common practice and can lead to leukoencephalopathy. CONCLUSIONS: Leukoencephalopathy associated with heroin inhalation is a rare entity that mainly affects young adults and has a high social impact. Its aetiology is unclear, it has no effective treatment and there is a high mortality rate. Heroin consumption is on the rise in Colombia, so TL should be considered by medical staff.

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 poisoning, intentional self-harm and event of undetermined intent mortality over 20 years in Iceland: a population-based cohort study.

OBJECTIVES: The aim was to study mortality due to suicide, accidental poisoning, event of undetermined intent and drug-related deaths through 20 years in Iceland. DESIGN: A population-based register study. PARTICIPANTS: Individuals who died due to road traffic injury, suicide, accidental poisoning, event of undetermined intent and drug-related deaths in the population of Iceland during the years 1996-2015. Annual age-standardised rates were calculated, and the trend analysed by Pearson correlation and joinpoint regression. SETTING: The population of Iceland framed the study material, and the data were obtained from nationwide registries for information on number of deaths and age-specific mean population in each year by gender. RESULTS: The crude overall suicide rate during the last 10 years was 12.2 per 100 000 persons per year (95% CI 7.4 to 18.1), while the crude overall rate due to road traffic injuries was 4.6 per 100 000 persons per year (95% CI 2.0 to 8.3). Among men, suicide rates decreased, however not significantly (r(19)=-0.22, p=0.36), and for overdose by narcotics the rates increased significantly (r(19)=0.72, p<0.001) during the study period. Among women, the suicide rates increased, however not significantly (r(19)=0.35, p=0.13), for accidental poisoning, suicide and event of undetermined intent combined the rates increased significantly (r(19)=0.60, p=0.006); and the rates for overdose by sedative and overdose by narcotics both increased significantly r(19)=0.49, p=0.03, and r(19)=0.67, p=0.001, respectively. CONCLUSION: The suicide rates have not changed during 1996 to 2015; however, the rates for the combined accidental poisoning, suicide and event of undetermined intent increased significantly for women. The rise of the overdose rates for sedative among women and for narcotics among both genders are consistent with reports elsewhere.

Importance and Approach to Manner of Death Opinions in Opioid-Related Deaths.

The majority of opioid-related deaths are accidental. However, the number of opioid-related suicidal deaths is likely under recognized. Presented here is a case of suicide by heroin overdose. The manner of death would have likely been deemed accidental if not for critical information shared by the decedent's family during follow-up telephone interviews between the forensic pathologist and the decedent's family, which included text messages that were sent by the decedent just before his death that were not known at the time of the initial medicolegal death scene investigation. This case highlights that when a forensic pathologist establishes an engaged relationship with the decedent's family, the information elucidated can prove to be invaluable in reaching an informed opinion about the manner of death. For overdose cases, identifying an accurate manner of death allows the design of public health efforts that adequately address the health risks in the community. For aid in the determination of the manner of death for overdose cases, we propose a five-step checklist that may assist forensic pathologists and medicolegal death investigators when approaching similar cases.

Evidence of fentanyl use is common and frequently missed in a cross-sectional study of emergency department patients in Baltimore, Maryland.

Objective: Fentanyl-associated deaths have risen in Maryland, but the prevalence of illicit fentanyl use is unknown. Our objective was to measure whether fentanyl is present among emergency department (ED) patients seeking care for a drug overdose.Design: The prevalence of fentanyl use was determined using a cross-sectional study of a convenience sample of adult ED patients with complaints of apparent opioid overdose, withdrawal from opioids, and/or requesting treatment for their substance use disorder (SUD) between February and April, 2018. Subjects were consented, interviewed, and underwent urine point-of-care (POC) fentanyl testing.Results: A total of 102 patients met inclusion criteria and were approached, 76 consented, 63 (83%) of whom tested positive for recent fentanyl use. 60 (80%) were male, 26 (34%) had overdosed, 41 (54%) were seeking SUD treatment, and 13 (17%) were in withdrawal (4 had multiple complaints). Of those who underwent both standard hospital urine drug screen and POC fentanyl testing, 56% (22/39) were positive for fentanyl and negative for opiates. Only 5% (4/76) reported knowledge of using fentanyl.Conclusions: Fentanyl use was common and frequently missed among these ED patients. Hospitals who treat patients taking illicit fentanyl should consider adding fentanyl to their urine drugs of abuse panel.

Validating Imputation Procedures to Calculate Corrected Opioid-Involved Overdose Deaths, Marion County, Indiana, 2011-2016.

OBJECTIVES: Understanding the scope of the current opioid epidemic requires accurate counts of the number of opioid-involved drug overdose deaths. Given known errors and limitations in the reporting of these deaths, several studies have used statistical methods to develop estimates of the true number of opioid-involved overdose deaths. This study validates these procedures using a detailed county-level database of linked toxicology and vital records data. METHODS: We extracted and linked toxicology and vital records data from Marion County, Indiana (Indianapolis), during a 6-year period (2011-2016). Using toxicology data as a criterion measure, we tested the validity of multiple imputation procedures, including the Ruhm regression-based imputation approach for correcting the number of opioid-involved overdose deaths. RESULTS: Estimates deviated from true opioid-involved overdose deaths by 3% and increased in accuracy during the study period (2011-2016). For example, in 2016, 231 opioid-involved overdose deaths were noted in the toxicology data, whereas the corresponding imputed estimate was 233 opioid-involved overdose deaths. A simple imputation approach, based on the share of opioid-involved overdose deaths among all drug overdose deaths for which the death certificate specified ≥1 drug, deviated from true opioid-involved overdose deaths by ±5%. CONCLUSIONS: Commonly used imputation procedures produced estimates of the number of opioid-involved overdose deaths that are similar to the true number of opioid-involved overdose deaths obtained from toxicology data. Although future studies should examine whether these results extend beyond the geographic area covered in our data set, our findings support the continued use of these imputation procedures to quantify the extent of the opioid epidemic.

[Poisoning by addictive substances, laboratory tests, and forensic medical death clarification in the case of poisoning]. / Vergiftungen durch Suchtstoffe, Laboruntersuchungen und rechtsmedizinische Todesfallaufklärung bei Vergiftungen.

Clinical-toxicological investigations are very helpful for the detection and assessment of the severity of questionable narcotics intoxications. In some cases, an initial case of clinical poisoning then progresses in the further course to a case of forensic relevance (for example after deliberate poisoning e.g, with knock-out drugs or with intend to commit murder, or in cases of intoxication in connection with a criminal offense).The specifics and problems of the analytical detection of these substances in clinical and forensic cases are explained with regard to the presented narcotic drugs. The information used comes from data from our own examination material and data from the literature.The spectrum of addictive substances has changed significantly in recent years. While established methods of detection are available for alcohol and classic drugs of abuse, new drugs with potential for abuse (such as methylphenidate, pregabalin) or NPS, GHB, GBL, and 4­BD cannot be detected by conventional methods of immunochemistry in combination with chromatographic methods such as GC-MS and HPLC-DAD.An improvement in the measurement equipment for specialised laboratories performing such investigations is therefore required in order to be able to adequately care for patients and to clarify criminal offenses. In the interests of legal certainty, it is important for offenders, in the case of a foreign substance being supplied to a victim, to assume that it can also be proven. In addition, with regard to the reliability of officially stated prevalence data for narcotic drugs in drug-related deaths, greater safety should be sought in the collection of all relevant substances.

[Overdose deaths from narcotic drugs and psychotropic substances in Russia (an analysis of materials for the period 2003 to 2018)]. / Smertel'nye otravleniia narkoticheskimi sredstvami i psikhotropnymi veshchestvami v Rossii (po materialam 2003-2018 gg.).

The purpose of the work is to study the prevalence of overdose deaths from narcotic drugs and psychotropic substances in Russia, as determined by forensic autopsies, for the period 2003 to 2018. For the study, medical statistics were processed, the percentages for each indication were calculated, and the changes in the percentages for different types of overdose deaths were noted. It was established in forensic autopsies for the period under study, that the percentage of narcotic overdose deaths ranged from 4.2% to 16.6% of the total number of poisonings, while the percentage of overdose deaths from psychotropic substances ranged from 0.7% to 1.3%.

[The use of biochemical characteristics of cadaveric blood in the forensic diagnosis of lethal poisoning]. / Ispol'zovanie nekotorykh sudebno-biokhimicheskikh pokazatelei trupnoi krovi pri diagnostike letal'nykh otravlenii.

The purpose of the work is the development of mathematical models in the forensic diagnosis of poisonings by the main groups of toxicologically important substances, on the basis of biochemical characteristics of blood. The most informative forensic and biochemical indicators of cadaveric blood used to detect lethal poisoning are the urea content, total protein content, and the ratio of urea to creatinine. Mathematical models of poisoning can be used to diagnose poisoning with narcotic drugs, psychotropic substances and substitutes of ethyl alcohol.

[Analysis of fatal cases of psychoactive drug overdoses in the Crimean Republic between 1993-2017]. / Analiz smertel'nykh otravlenii psikhoaktivnymi veshchestvami v Respublike Krym za 1993-2017 gg.

An analysis of fatal drug overdoses in the population of the Crimean Republic between 1993-2017 was conducted. The epidemiological characteristics of these drug overdoses were determined. Deaths from drug overdoses occurs mainly in male population during the most active years of drug use (21-30 years). The most frequent cause of death is opioid drug overdose and combined alcohol-opioid intoxication.

Relay: A Peer-Delivered Emergency Department-Based Response to Nonfatal Opioid Overdose.

Relay, a peer-delivered response to nonfatal opioid overdoses, provides overdose prevention education, naloxone, support, and linkage to care to opioid overdose survivors for 90 days after an overdose event. From June 2017 to December 2018, Relay operated in seven New York City emergency departments and enrolled 649 of the 876 eligible individuals seen (74%). Preliminary data show high engagement, primarily among individuals not touched by harm reduction or naloxone distribution networks. Relay is a novel and replicable response to the opioid epidemic.

Rise in mortality involving poisoning by medicaments other than narcotics, including poisoning by psychotropic drugs in different age/racial groups in the US.

BACKGROUND: Increase in mortality involving poisoning, particularly by narcotics, is known to have been one of the factors that affected life expectancy in the US during the last two decades, especially for white Americans and Native Americans. However, the contribution of medicaments other than narcotics to mortality in different racial/age groups is less studied. METHODS: We regressed annual rates of mortality involving poisoning by medicaments but not narcotics/psychodysleptics (ICD-10 codes T36-39.xx or T41-50.8 but not T40.xx present as either underlying or contributing causes of death), as well as annual rates of mortality for certain subcategories of the above, including mortality involving poisoning by psychotropic drugs but not narcotics/psychodysleptics (ICD-10 codes T43.xx but not T40.xx present as either underlying or contributing causes of death) in different age/racial groups for both the 2000-2011 period and the 2011-2017 period against calendar year. RESULTS: Annual numbers of deaths involving poisoning by medicaments but not narcotics/psychodysleptics grew from 4,332 between 2000-2001 to 11,401 between 2016-2017, with the growth in the rates of those deaths being higher for the 2011-2017 period compared to the 2000-2011 period. The largest increases in the rates of mortality involving poisoning by medicaments but not narcotics/psychodysleptics were in non-elderly Non-Hispanic Native Americans, followed by Non-Hispanic whites. Most of those increases came from increases in the rates of mortality involving poisoning by psychotropic medications; the latter rates grew for the period of 2015-2017 vs. 2000-2002 by factors ranging from 2.75 for ages 35-44y to 5.37 for ages 55-64y. CONCLUSIONS: There were major increases in mortality involving poisoning by non-narcotic, particularly psychotropic medicaments, especially in non-elderly non-Hispanic whites and Native Americans. Our results support the need for a comprehensive evaluation of the effect of psychotropic medications on health-related outcomes, including mortality for causes other than poisoning, and the impact of medication misuse.

Epidemiology of severe buprenorphine exposures reported to the U.S. Poison Centers.

OBJECTIVE: This study aims to evaluate the trends and risk factors of severe buprenorphine outcomes (SBO) reported to the U.S. Poison Centers (PCs). METHODS: We queried the National Poison Data System for exposures to buprenorphine from 2011 to 2016. SBO cases were defined as exposures that resulted in either a death or major clinical outcomes. Trends were tested using Poisson regression. Characteristics of the exposures were descriptively assessed. Logistic regression was used to evaluate the risk factors of SBO. RESULTS: SBO cases (967) reported to the PCs increased by 66.6% during this period (114-190, p < 0.001). While adults between 20 and 39 years were more frequent in the SBO group (50.4%) compared to the non-SBO group (38.7%), cases under 6 years (29.6% vs 13.8%) were more common among the non-SBO group. Intentional abuse (20.1% vs 24.9%) and suspected suicides (13.7% vs 37.5%) were significantly higher among the SBO group. Multisubstance exposures were more frequent among the SBO cases (36.4% vs 71.4%). SBO risk increased with age, with cases above 60 years (AOR: 1.66, 95% CI: 1.14-2.42) demonstrating significantly increased odds. Suspected suicide (AOR: 1.87, 95% CI: 1.53-2.28) and abuse (AOR: 1.40, 95% CI: 1.13-1.73) cases were more likely to result in a SBO. Multisubstance exposures significantly increased the risk of a SBO. CONCLUSIONS: This study reflected an increase in the cases of SBO paralleling the rise in the buprenorphine prescriptions. Age, reasons for exposure and multi-substance exposures significantly increased the risk of SBO.

Opium poisoning in modern times. An overview.

Opium is a substance extracted from Papaver somniferum L that is chronically abused specially in the traditional production regions. Reports on opium poisoning has largely disappeared from the occidental literature on drug problems but recent scientific articles show cases of death related to opium in industrialized countries. This fact led us to consider the interest of knowing the state of the art of acute opium intoxication in modern times. This work shows a compilation of these uncommon cases occurred in different settings and circumstances. Data were obtained by a computer assisted search of the literature using the key words "opium poisoning", "poppy", "poppy seeds", and "papaver somniferum" in PubMed, accompanied by a hand search of the reference lists of all articles for any relevant studies not included in the database. In addition, Google Scholar, government reports, and cases adequately documented on websites were reviewed. Type 1 cases, Accidental opium intoxications when it is used as a recreational drug: Reported cases came mainly from industrialized countries. They were mostly male with a range age of 17-64 years. Many had antecedents of alcoholism or drug abuse and opium tea was used as a substitute of heroin. Rachacha has caused poisonings in France and has been detected in a stash in Spain. Toxicological analysis was documented in forensic cases. The danger of this renewed interest in opium is exemplified in that many of the poisoning cases resulted in fatalities. Type 2 cases, Accidental opium intoxications in children or adults when it used as folk remedy: Pediatric intoxication after the use of opium as folk remedy are mainly published in traditional opium-producing areas with a long history of use or ethnic communities in England or USA. Addiction to opium was common among relatives. Type 3 cases, Opium intoxications with poppy seeds consumed as food: Due to excessive consumption of opium seeds as food, sporadic cases of mild toxicity had been reported and morphine contents were documented. Type 4 cases: Accidental opium intoxications when using the abdominal or pelvic cavity for concealing the drug: Accidental opium body packer intoxications are seen in patients who traveled from illegal opium areas of production. Type 5 cases: Suicides by opium: Opium was a prevalent agent among cases of suicides in Iran but data are scarce.