Teens and Spice: A Review of Adolescent Fatalities Associated with Synthetic Cannabinoid Use

Synthetic cannabinoids (SCs) are commonly abused by adolescents with reported past year (2013) use in high school students between 3 and 10%. Standard adolescent postmortem toxicology does not include routine SC analysis, and thus, the true burden of fatalities related to SCs is unknown. A retrospective case review of two cases included scene investigation, interviews, autopsy, and toxicology. SCs were confirmed by liquid chromatography–tandem mass spectrometry (LC?MS/MS). Review of the eight adolescent SC‐associated fatalities in the literature revealed five of eight cases had no other discernible cause of death on autopsy. Compounds detected included PB‐22 (1.1 ng/mL), JWH‐210 (12 ng/mL), XLR‐11 (1.3 ng/mL), JWH‐122, AB‐CHMINACA (8.2 ng/mL), UR‐144 (12.3 ng/mL), and JWH‐022 (3 ng/mL). With synthetic drug use on the rise, forensic experts should have a high index of suspicion for the possibility of SC intoxication in adolescent fatalities with no other discernible cause of death.     

Methadone determination in puparia and its effect on the development of Lucilia sericata (Diptera, Calliphoridae)

This paper describes a sensitive UPLC-MS/MS method for quantification of methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) in single empty puparial case of Lucilia sericata. Larvae were reared on substrates spiked with different concentrations of methadone (0-4 μg/g). Methadone was quantified in puparia reared on high concentrated substrates (0.8-4 μg/g). The major metabolite of methadone (EDDP) was not detected, confirming rapid elimination of metabolites by the larvae before pupation. The effects of methadone on the development of L. sericata were also investigated. No effect on sex ratio was detected. A significant difference was calculated for emerged adults but no trends could be observed. Concerning the developmental curve, a significant difference was observed between control and high methadone concentrations using the Kolmogorov-Smirnov test.     

Pharmacogenomics as an aspect of molecular autopsy for forensic pathology/toxicology: does genotyping CYP 2D6 serve as an adjunct for certifying methadone toxicity?

Pharmacogenomics, applied as an aspect of molecular autopsy, may be used as an adjunct for certifying methadone fatalities. Methadone is metabolized by cytochrome P-450 (CYP) 1A2, 3A4, and 2D6. We hypothesized that methadone toxicity may be partially due to CYP 2D6 *3, *4, and *5 variant alleles, resulting in poor drug metabolism. A retrospective analysis was performed on covariables and risk factors of 21 methadone cases from the Milwaukee County Medical Examiner's Office (1998-2000). PCR genotyping showed: one heterozygous for 2D6*3, two homozygous for 2D6*4, five heterozygous for 2D6*4, and one heterozygous for both 2D6*3 and *4. This limited number of cases showed that the prevalence of poor metabolizer was higher but not significantly different from that of a control group (n = 23) (P > 0.05, Fisher Exact Test). Thus, CYP 2D6 mutations may not yet be directly associated with methadone toxicity. However, pharmacogenomics, complementing other case findings, served as an adjunct in interpreting methadone toxicity of poor and intermediate metabolizers.     

Fatal diphenhydramine intoxication in infants

Diphenhydramine is an antihistamine available in numerous over-the-counter preparations. Often used for its sedative effects in adults, it can cause paradoxical central nervous system stimulation in children, with effects ranging from excitation to seizures and death. Reports of fatal intoxications in young children are rare. We present five cases of fatal intoxication in infants 6, 8, 9, 12, and 12 weeks old. Postmortem blood diphenhydramine levels in the cases were 1.6, 1.5, 1.6, 1.1 and 1.1 mg/L, respectively. Anatomic findings in each case were normal. In one case the child's father admitted giving the infant diphenhydramine in an attempt to induce the infant to sleep; in another case, a daycare provider admitted putting diphenhydramine in a baby bottle. Two cases remain unsolved; one case remains under investigation. The postmortem drug levels in these cases are lower than seen in adult fatalities. We review the literature on diphenhydramine toxicity, particularly as it pertains to small children, and discuss the rationale for treating these cases as fatal intoxications.     

Toxicological Analysis of Opiates from Alternative Matrices Collected from an Exhumed Body

In this case study, the body of a 45‐year‐old man was exhumed after 1 year at the request of the public prosecutor to assess whether the death was caused by drug consumption. Toxicological analyses were performed on several matrices, including liver, kidney, and the alternative matrices hair and teeth. The systematic toxicological analysis (STA), which consisted of basic and acid liquid/liquid extraction and gas chromatography–mass spectrometry (GC‐MS) analysis, showed the presence of opiates in each of the matrices analyzed. Subsequently, to confirm and quantify the presence of opioids, samples of each of the matrices were subjected to solid‐phase extraction and specific GC‐MS analysis. The case presented demonstrates the possibility of drug detection in an exhumed body that has been buried for 1 year, despite the problems of quantitative interpretation of the data, and that toxicological results could be useful along with other forensic evidence.     

Machinery‐Related Deaths: Relevance of Workplace Investigation and Antemortem Radiological Data in Reconstructing the Fatality

Abstract: Machinery‐related fatalities are one of the leading causes of traumatic occupational deaths. In our report, we present the case of a 40‐year‐old male who suffered a severe head trauma while working in a cut‐foam industry and died despite an early craniectomy. The radiological reconstruction of the skull based on preoperative computed tomography scans disclosed a large depressed conical fracture of the left parietal bone. The 3D‐reconstruction of the work area, combined with a fit‐matching analysis between the machinery and the depressed skull fracture allowed us to conclude that the head was crushed between the sliding bar of the cutting device and the metallic protuberance on the opposite side. The case underlines the importance of a detailed workplace investigation and of a thorough evaluation of all circumstantial, clinical, radiological, and autopsy data in the reconstruction of machinery‐related fatalities to identify any possible legal responsibilities of the worker and/or the employer.     

A review of methadone deaths in Jefferson County,Alabama

Interpretation of the concentration of a drug is more difficult when a combination of drugs is present in a decedent's blood. An increase in deaths resulting from co-intoxication with methadone and a benzodiazepine led the authors to perform a retrospective study of cases examined at the Jefferson County Coroner/Medical Examiner Office. They found 101 deaths wherein methadone was detected in the blood. Based on the drugs detected in the blood, these 101 cases were grouped into four categories: (1) pure methadone intoxication, (2) intoxication with methadone and benzodiazepine, (3) intoxication with methadone and other drugs excluding benzodiazepine, and (4) intoxication with methadone, benzodiazepines, and other drugs. Methadone was the sole intoxicant in 15 cases, with a mean concentration of 0.27 mg/L. Benzodiazepines were the most frequently detected co-intoxicant (60 of 101 cases). Benzodiazepine was the only co-intoxicant in 30 cases, and the mean methadone concentration in those 30 cases was 0.599 mg/L. Higher levels of methadone may occur in acute intoxication with methadone and benzodiazepine because benzodiazepines compete with methadone for methadone receptors. Higher levels of methadone may occur with chronic abuse of methadone and benzodiazepines because over time, benzodiazepines inhibit the hepatic enzymes that metabolize methadone.     

Autoerotic asphyxiation in a female

Autoerotic asphyxiation is an unusual but increasingly more frequently occurring phenomenon, with >1000 fatalities in the United States per year. Understanding of this manner of death is likewise increasing, as noted by the growing number of cases reported in the literature. However, this form of accidental death is much less frequently seen in females (male:female ratio >50:1), and there is correspondingly less literature on female victims of autoerotic asphyxiation. The authors present the case of a 31-year-old woman who died of an autoerotic ligature strangulation and review the current literature on the subject. The forensic examiner must be able to discern this syndrome from similar forms of accidental and suicidal death, and from homicidal hanging/strangulation.     

Identification of furosemide in hair in a post‐mortem case by UHPLC‐MS/MS with guidance on interpretation

Testing for drugs in hair raises several difficulties. Among them is the interpretation of the final concentration(s). In a post‐mortem case, analyses revealed the presence of furosemide (12 ng/mL) in femoral blood, although it was not part of the victim's treatment. The prosecutor requested our laboratory to undertake an additional analysis in hair to obtain information about the use of furosemide. A specific method was therefore developed and validated to identify and quantify furosemide in hair by UHPLC‐MS/MS. After decontamination of 30 mg of hair, incubation in acidic condition, extraction with ethyl acetate, the samples were analyzed by UHPLC‐MS/MS. Furosemide was found in the victim's hair at 225 pg/mg. However, it was not possible to interpret this concentration due to the absence of data in the literature. Therefore, the authors performed a controlled study in two parts. In order to establish the basis of interpretation, several volunteers were tested (four after a single 20 mg administration and twenty‐four under daily treatment). The first part indicated that a single dose is not detectable in hair using our method. The second part demonstrated concentrations ranging from 5 to 1110 pg/mg with no correlation between dosage and hair concentrations. The decedent's hair result was interpreted as repeated exposures. In the case of furosemide analysis, hair can provide information about its presence but cannot give information about dosage or frequency of use.     

Methadone-related deaths in Hennepin County,Minnesota: 1992-2002

Methadone maintenance therapy (MMT) is the only currently established medical therapy for heroin addiction. However, MMT still remains controversial. In Hennepin County, Minnesota, methadone is one of the top ten drugs reported in medical examiner investigated deaths and one of the most commonly diverted pharmaceuticals. This report reviews the role of methadone in medical examiner deaths over a 10-year period, 1992-2002. We compare cause and manner of death (accidental, natural, suicide) and methadone blood concentrations for decedents who were members of MMT programs with illicit users and those prescribed methadone for chronic pain. Findings reveal that 65% of decedents with measurable blood methadone concentrations were not participating in MMT programs. A total of 96 cases were identified, with the majority white (90.5%) and male (76.8%). MMTP program members were the minority (34.7%) of the methadone positive deaths and 39% were illicit users. Fifteen percent were chronic pain patients with almost half of this group dying from overdose. Methadone concentrations of drug caused/related deaths (0.18-3.99 mg/L) overlapped with those of deaths not attributable to methadone (0.18-3.03 mg/L) with no definable lethal level. Interpretation of methadone blood concentrations must be done in the context of the clinical history for determining cause of death, and may be confounded by postmortem redistribution.     

Determination of methadone in urine using ion trap GC/MS in positive ion chemical ionization mode

Methadone is a potent analgesic and sedative. It is widely used in the treatment of heroin addiction and is often encountered in forensic specimens. In electron impact (EI) gas chromatography/mass spectrometry (GC/MS) mode, methadone produces predominantly a m/z 72 ion, which is not sufficiently characteristic for identification. Determination of the molecular ion, which can be achieved using chemical ionization (CI) provides diagnostic information and better identification of the drug. This paper describes the development of a positive ion CI GC/MS procedure, using a liquid reagent gas and ion trap instrumentation, for the determination of methadone and its metabolites in urine. CI generally produces a single molecular ion spectrum, but optimization of the reagent gas parameters increases the fragmentation of the molecule, allowing determination of ion ratios if required. The procedure is sensitive, diagnostic and is currently in routine use in our laboratory.     

Motor Vehicle Occupants,Neck Injuries,and Seat Belt Utilization: A 5‐Year Study of Fatalities in New York City

Abstract: Despite the implementation of numerous safety devices in automobiles, vehicular occupant fatalities following collisions remain common. We reviewed all fatalities of vehicular occupants in New York City over a 5‐year period on whom autopsies were performed (437) to determine the incidence of neck injuries and correlate them with seat belt utilization; 26.5% had neck injuries (mild to severe) and only 10.3% of these occupants were confirmed to be wearing seatbelts. Of those that had documentation of seat belt utilization there were twice as many neck injuries in the unbelted group. We highlight two cases of submarining with severe neck injuries that were related to automatic 2‐point shoulder harness restraints without engagement of the lap belt.     

n‐Ethyl Pentylone‐Related Deaths in Alabama

n‐Ethyl pentylone (NEP) is a chemical substance derived from cathinone. Synthetic cathinones are an evolving group of drugs with stimulating, mind‐altering effects sometimes referred to as novel or new psychoactive substances (NPS). There is scarce information in the medical literature regarding forensic cases in which NEP is detected in toxicological testing. We present four fatalities involving NEP from Alabama in 2017. Deaths were attributed to NEP toxicity in two cases (peripheral blood concentrations of 0.121 and 0.953 mg/L) and injuries caused by gunshot wounds in two cases (peripheral blood concentrations of 0.045 and 0.031 mg/L). One case involving NEP described an individual who exhibited classic CNS‐stimulant induced erratic behavior before being found dead. These cases enhance the forensic literature regarding specific NPS like NEP and provide contextual reference for professionals considering the significance of NEP in toxicological interpretation.     

Fatal Injuries of Law Enforcement/Correctional Officers Attacked with Sharp‐Edged Weapons,

According to the National Law Enforcement Memorial Fund, there were 117 law enforcement fatalities in the United States in 2015. Assaults with sharp‐edged weapons have resulted in a total of over 400 fatalities in the United States. The goal of the current research was to examine sharp‐edged weapon assaults against law enforcement and correctional agents that resulted in a fatal outcome. A total of twelve autopsy reports were reviewed from across the United States. Four cases involved law enforcement officers, seven involved correctional officers, and one was an off‐duty border officer. The male‐to‐female ratio was 11:1. A total of 70.2% of the wounds analyzed were stab wounds (n = 85), and 29.8% of the wounds were slash wounds (n = 36). Based on this review, the neck, shoulder, and chest regions were the most vulnerable to single fatal stab/slash wounds. Multiple stab/slash wounds often resulted in exsanguination. The use of body armor was only noted in one case.     

Fatal Case of a 27‐Year‐Old Male After Taking Iboga in Withdrawal Treatment: GC‐MS/MS Determination of Ibogaine and Ibogamine in Iboga Roots and Postmortem Biological Material

We report the case of a man who died twelve hours after ingesting powdered iboga root, commonly taken for its stimulant and hallucinogenic properties. Ibogaine and ibogamine were quantified in the powder ingested and the victim's body fluids by GC‐MS/MS after liquid–liquid extraction (Toxi‐tubes A^®). The concentrations of ibogaine measured in the blood samples taken at the scene and in the peripheral blood, urine, and gastric fluid samples taken during the autopsy were 0.65, 1.27, 1.7, and 53.5 μg/mL, while the iboga content in the powder was 7.2%. Moreover, systematic toxicological analyses of biological samples showed the presence of diazepam and methadone in therapeutic concentrations. Death was attributed to the ingestion of a substantial quantity of iboga in the context of simultaneous methadone and diazepam consumption.