Fatal Intoxications in a Forensic Autopsy Material from Epirus,Greece, During the Period 1998‐2010

In this retrospective study, we report the epidemiological characteristics of all poisoning deaths in Epirus, Greece, from 1998 to 2010; we present the toxicological findings and the statistical evaluation of the results. This is the first detailed scientific report on all the officially certified poisoning deaths concerning part of the Greek population. A total of 126 poisoning fatalities were recorded, 67 of them being mono‐intoxications (53.2%). The cause of poisoning was as follows: drugs of abuse (60%); carbon monoxide (19.8%); pesticides (9.5%); corrosives (4.8%); pharmaceuticals (4.8%); and spider bite (0.8%). The most frequently detected poisonous substances were as follows: heroin (65 cases), ethanol (55), benzodiazepines (42), carbon monoxide (25), cocaine (17), cannabinoids (17) and pesticides (12). Increasing tendency in poisoning death rates was recorded, due to an increase in accidental poisoning deaths attributed mainly to drugs of abuse (total, accidental, and drugs‐of‐abuse poisoning death rates per 100,000 inhabitants per year were 1.87, 1.19, and 0.79, respectively, in the period 1998–2002 and 3.97, 3.41, and 2.55, respectively, in the period 2007–2010).     

Determining the Toxicological Significance of Pregabalin in Fatalities

Pregabalin has become more widely prescribed and abused in recent years but is still not always included in laboratory analysis. An LC‐MS‐MS method has been developed and applied to measure pregabalin in 93 postmortem cases, including drug‐related deaths, alternative causes of death, and fatalities where pregabalin was likely to have contributed to death. Other drugs or alcohol was detected, and the most common drug types (in decreasing frequency) were antidepressants, opioids, benzodiazepines, opiates, alcohol, antipsychotics, cocaine, cardiac drugs, amphetamines, cannabis, anticonvulsants, and antihistamines. New psychoactive substances (methoxphenidine and synthetic cannabinoids) were only found in two cases. The results provide further data to assist in evaluating the significance of postmortem pregabalin concentrations and a toxicologically significant concentration of 25 mg/L is proposed. Pregabalin, especially with concomitant use of other CNS depressant drugs, presents a significant toxicological risk and existing laboratory protocols should be reviewed for their suitability to detect pregabalin.     

The designer drug situation in Ibiza

A total of 137 urine samples and 46 serum samples, corresponding to 154 self-confessed designer drugs consumers in Ibiza island, were analyzed for the presence of designer drugs: amphetamine and amphetamine derivatives (methamphetamine, methylenedioxymethamphetamine (MDMA), methylenedioxyethylamphetamine (MDEA), methylenedioxyamphetamine (MDA), p-methoxymethylamphetamine (PMMA), p-methoxyamphetamine (PMA), etc.), ketamine and γ-hydroxybutyric acid. Among this population, coming both from the forensic clinic and from the emergency room of a hospital, a total of 99 cases were found positive for some designer drug. This study shows the prevalence of methylenedioxymethamphetamine (MDMA) among designer drug users, sole or in association with other drugs. Also, the mixture of MDMA with other designer drugs, ethanol and/or cocaine is shown to be more likely to produce toxic symptoms requiring clinical attendance in a hospital emergency room. These findings along with the consumption history, the concentrations of drugs and metabolites in urine and serum and the toxicological significance for the interpretation of some MDMA metabolites such as 4-hydroxy-3-methoxymethamphetamine (HMMA) are discussed in this study.     

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.     

A study of drug detection in a postmortem pediatric population

At The Office of the Cuyahoga County Coroner (CCCO), Cleveland, Ohio, it is customary to perform an autopsy and conduct toxicological testing on decedents less than 19 years of age. This study provides a retrospective evaluation of drugs detected in a pediatric postmortem population between the years 1998 and 2002 (n = 730). Demographic information, cause and manner of death, and toxicological results were examined. Blacks comprised 54% of cases, males 59%, and 48% were less than one year of age or stillborn. Forty-two percent of deaths were ruled natural, 27% accident, 13% undetermined, 5% suicide, and 2% homicide. Of the 640 cases subjected to comprehensive testing, 38% of the cases were positive for at least one compound. Resuscitative/treatment drugs were detected most frequently (56% of positive results), followed by illicit drugs (26%), ethanol (11%), carbon monoxide (8%), and antihistamines (6%). Eighty-seven cases contained more than one drug. The deaths of 47 individuals were drug related (6%). In this population, it is recommended that illicit drugs and ethanol are targeted for testing, especially when limited specimens are available for analysis.     

Trends and pattern of drug abuse deaths in Maryland teenagers

The Office of the Chief Medical Examiner of Maryland recorded a total of 149 drug abuse deaths of teenagers aged 13-19 years between 1991 and 2006. Of these deaths, 96 (64.4%) were caused by the use of narcotic drugs only, 29 (19.5%) by both narcotics and cocaine, four (2.7%) by both narcotics and methylenedioxymethamphetamine, six (4.0%) by cocaine only, and 14 (9.4%) by volatile substances (e.g., butane, Freon, nitrous oxide, and propane). The annual death rate from drug abuse for teenagers increased from 1.4 deaths per 100,000 population in 1991 to 2.7 deaths per 100,000 population in 2006 (chi-square test for time trend, p<0.01). The increase in teenager drug abuse deaths occurred in 1999 and since has remained at a higher rate. Further analysis revealed that the increase in drug abuse deaths was attributable to a large degree to narcotic drugs, particularly heroin/morphine and methadone, and was confined to teenagers residing in the suburban and rural areas.     

Toxicology and Circumstances of Death of Homicide Victims in New South Wales, Australia 1996–2005

Abstract:  To determine the prevalence and circumstances of psychoactive substances amongst homicide victims, 485 consecutive cases autopsied at the NSW Department of Forensic Medicine (1/1/1996–12/31/2005) were analyzed. Substances were detected in 62.6% of cases, and illicit drugs in 32.8%. Alcohol, cannabis, opioids, and psychostimulants were most commonly detected. Alcohol and cannabis were both more prevalent amongst males. Mean ages were significantly younger for decedents who tested positive for a substance and for an illicit drug. Cases where death resulted from a physical altercation were more likely to have had alcohol and cannabis present. Illicit drugs were prominent amongst firearms deaths. The proportion of alcohol positive cases increased from 25.0% on Monday to 49.4% for Saturdays/Sundays. Alcohol was more common in incidents in the 0001–0600 h and 1800–2400 h periods. Psychoactive substances appear to substantially increase the risk of homicide, although there are important differences between drug classes in the circumstances of such incidents.     

Measurement of drugs in neonatal hair; a window to fetal exposure

Because the hair neonates are born with grows during the last 3 months of pregnancy, the presence of drugs (e.g. cocaine) or environmental toxins (e.g. nicotine) reflects fetal exposure to such compounds. In the case of cocaine, hair measurement are several fold more sensitive than maternal history or urine measurements. Measurements of cotinine in neonatal hair are capable of distinguishing between fetal exposure to passive versus active smoking. Because most cocaine users also smoke cigarettes, neonatal measurements of both cocaine and cotinine will allow cumulative quantification of fetal risk.     

Hair analysis of opiates in mothers and newborns for evaluating opiate exposure during pregnancy

The increasing interest in toxicological hair analysis as a marker of human exposure to xenobiotics such as illicit substances or therapeutic drugs, has been made feasible by the extension of mass spectrometry, a highly sensitive method of detection. A newborn exposed to drugs in utero can suffer from a varying degree of withdrawal syndrome, a few days after birth. If of opiate origin, the withdrawal syndrome can be treated with morphine, among other therapeutics, but it is not easy to diagnose because of atypical symptoms presented by neonates and especially when maternal drug addiction has not been revealed. To assess and measure toxicological factors linked with the appearance and the severity of this syndrome, maternal and neonatal matrices such as urine, meconium and hair were collected during a protocol approved by the ethical committee. Opiates in particular were measured with GC-MS and potential combined dependences (cannabis, cocaine, amphetamine, LSD and benzodiazepines) and/or substitutive therapeutics (methadone or buprenorphine) were also assessed in 17 mother/neonate couples. Gestational opiate exposure profiles were drawn up and linked with the observed withdrawal syndromes. A withdrawal syndrome seems to appear more frequently after foetal exposure to an association of opiates/substitutive molecules (8 out of 10 withdrawal syndromes observed in this study), although the impact of cocaine and benzodiazepines must also be taken into account. The results obtained in neonatal hair make it possible to affirm foetal drug exposure and are in accordance, for the majority, with the appearance of a neonatal withdrawal syndrome (NWS). Neonatal hair analysis could contribute to assess in utero exposure to opiates, particularly when results in urine and meconium are negative or when these matrices are not available.     

Increased risk of fatal intoxication and polypharmacy among psychiatric patients at death

Patients suffering from psychiatric disorders have an excess mortality and a shorter life span expectancy compared to the general population. Furthermore, they are treated with multiple drugs and are known to have an increased risk of drug abuse. In this study, we aimed at investigating the pharmaceutical drug and drug of abuse profiles of the deceased included in the Danish prospective autopsy‐based forensic study on psychiatric patients, SURVIVE. Using the postmortem systematic toxicological analysis results, we identified 129 different consumed compounds in our population (n = 443). Polypharmacy (≥5 compounds) was detected in 39.5% of the deceased. Deceased with a psychiatric diagnosis or who died from a fatal intoxication had significantly more compounds at the time of their death compared to having either no psychiatric diagnosis or another cause of death, respectively. Evidence of drug abuse was present, as 29.8% of our total population had consumed either methadone or illicit drugs of abuse, excluding tetrahydrocannabinol. Of those deceased with a psychiatric diagnosis, 33.6% had either consumed methadone or illicit drugs of abuse, a greater number than those without a psychiatric diagnosis. Fatal intoxication was the most frequent cause of death (40.6%) with methadone as the major intoxicant. Here, we found that those without a psychiatric diagnosis had fewer fatal pharmaceutical drug intoxications compared to the psychiatric diagnosis groups. Our findings add further context to understanding the excess mortality of psychiatric patents, since there is an increased occurrence of fatal intoxication, polypharmacy, and drug abuse in this population.     

Ethanol, marijuana, and other drug use in 600 drivers killed in single-vehicle crashes in North Carolina, 1978-1981

Although the use of ethanol, marijuana, and other drugs may be detrimental to driving safety, this has been established by direct epidemiological evidence only for ethanol. In this study, the incidences of detection of ethanol (and other volatile substances), delta-9-tetrahydrocannabinol (THC), barbiturates, cocaine and benzoylecgonine, opiates, and phencyclidine were determined in an inclusive population of 600 verified single-vehicle operator fatalities that occurred in North Carolina in 1978 to 1981. The incidence of detection of amphetamines and methaqualone were determined for drivers accepted for study during the first two years (n = 340) and the last year (n = 260), respectively. Blood concentrations of 11-nor-deta-9-tetrahydrocannabinol-9-carboxylic acid (9-carboxy-THC) were determined in THC positive drivers. EMIT cannabinoid assays were performed on blood specimens from all drivers accepted for study during the third year, and the feasibility of using the EMIT cannabinoid assay as a screening method for cannabinoids in forensic blood specimens was investigated. The incidence of detection of ethanol (79.3%) was far greater than the incidences determined for THC (7.8%), methaqualone (6.2%), and barbiturates (3.0%). Other drugs were detected rarely, or were not detected. Blood ethanol concentrations (BECs) were usually high; 85.5% of the drivers whose bloods contained ethanol and 67.8% of all drivers had BECs greater than or equal to 1.0 g/L. Drug concentrations were usually within or were below accepted therapeutic or active ranges. Only a small number of drivers could have been impaired by drugs, and most of them had high BECs. Multiple drug use (discounting ethanol) was comparatively rare. Ethanol was the only drug tested for that appears to have a significantly adverse effect on driving safety.     

General unknown screening in hair by liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC-QTOF-MS)

The retrospective investigation of the exposure to toxic substances by general unknown screening of hair is still a difficult task because of the large number of possible poisons, the low sample amount and the difficult sample matrix. In this study the use of liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) was tested as a promising technique for this purpose. In the optimized procedure, 20mg hair were decontaminated with water and acetone and two times extracted by 18h incubation with 0.5ml of a mixture of methanol/acetonitrile/H(2)O/ammonium formate at 37°C. A mixture of deuterated standards from different drug groups was added for quantification and method control. The united extracts were evaporated to a residue of 0.5ml and 5μl were injected without clean-up for LC-QTOF-MS measurement (instrument Agilent 6530) with positive electrospray ionization and in data dependent acquisition mode. For peak identification the accurate mass data base and spectral library of the authors was used which contains accurate mass CID spectra of more than 2500 and theoretically calculated accurate mass data of more than 7500 toxicologically relevant substances. Validation at the example of 24 illegal drugs, their metabolites and benzodiazepines resulted in limits of detection of 0.003-0.015ng/mg, and limits of quantification of 0.006-0.021ng/mg with good accuracy and intra- and interday reproducibility. The matrix effect by ion suppression/enhancement was 72-107% for basic drugs and 42-75% for benzodiazepines. Yields of the hair extraction above 90% were determined for 59 drugs or metabolites. The method was applied to hair samples from 30 drug fatalities and from 60 death cases with known therapeutic drug intake at life time. Altogether 212 substances were identified with a frequency per drug of 1-40 (mean 4.2) and per case of 2-33 (mean 10.2), between them 35 illegal drug related substances and 154 therapeutic drugs. Comparison with the data known from case histories and from the analysis of blood, urine and gastric content showed only a low agreement, with many unexpected drugs detected and many reported drugs not detected in hair. Basic drugs and metabolites such as opioides, cocaine, amphetamines, several groups of antidepressants, neuroleptics, beta-blockers or the metamizole metabolite noramidopyrine were found with high frequency whereas acidic and several neutral drugs such as cannabinoids, salicylic acid, furosemide, barbiturates, phenprocoumone or cardiac glycosides could not be detected with sufficient sensitivity, mainly because of the low ion yield of positive ESI for these compounds. The advantage of a comprehensive acquisition of all substances is paid by a lower sensitivity in comparison to targeted screening LC-MS/MS procedures. In conclusion, the procedure of sample preparation and LC-QTOF-MS analysis proved to be a robust and sensitive routine method in which the qualitative screening for a wide variety of toxic substances in hair is combined with the quantitative determination of selected illegal drugs.     

Toxicological Findings in Fatal Motor Vehicle Collisions in Ontario,Canada: A One‐Year Study

Drug‐impaired driving is a complex area of forensic toxicology due in part to limited data concerning the type of drugs involved and the concentrations detected. This study analyzed toxicological findings in drivers from fatal motor vehicle collisions (FMVCs) in Ontario, Canada, over a one‐year period using a standardized protocol. Of the 229 cases included in the study, 56% were positive for alcohol and/or drugs. After alcohol, cannabis was the most frequently encountered substance (27%), followed by benzodiazepines (17%) and antidepressants (17%). There were differences in drugs detected by age but no marked difference in drugs detected between single and multiple FMVC's. Not all drugs detected were considered impairing either due to drug type, concentration or case history. The findings indicate the importance of comprehensive drug testing in FMVCs and highlight the need to consider a variety of factors, in addition to drug type and concentration, when assessing the role of drugs in driving impairment.     

Emergence of fentanyl-related deaths in Travis County,Texas and surrounding areas: A retrospective review of postmortem fentanyl-related drug toxicities from 2020 to 2022

The opioid epidemic has affected the United States (US) for decades with fentanyl and its analogs accounting for a recent surge in morbidity and mortality. Currently, there is a relative lack of information characterizing fentanyl-related fatalities specifically in the Southern US. A retrospective study was conducted to examine all postmortem fentanyl-related drug toxicities in Travis County, Texas, encompassing Austin (one of the fastest-growing cities in the US), from 2020 to 2022. Fentanyl contributed to 2.6% and 12.2% of deaths submitted for toxicology between 2020 and 2022, respectively, representing a 375% increase in fentanyl-related deaths over this 3-year period (n = 517). Fentanyl-related fatalities primarily occurred in males in their mid-30s. Fentanyl and norfentanyl concentrations ranged from 0.58 to 320 ng/mL and 0.53 to 140 ng/mL with mean (median) concentrations of 17.2 ± 25.0 (11.0) and 5.6 ± 10.9 (2.9) ng/mL, respectively. Polydrug use was present in 88% of cases, with methamphetamine (or other amphetamines) (25%), benzodiazepines (21%), and cocaine (17%) representing the most frequently identified concurrent substances. Co-positivity rates of various drugs and drug classes widely varied over time. Scene investigations reported illicit powder(s) (n = 141) and/or illicit pill(s) (n = 154) in 48% (n = 247) of fentanyl-related deaths. Illicit oxycodone (44%, n = 67) and illicit “Xanax” (38%, n = 59) pills were frequently reported on scene; however, toxicology only identified oxycodone and alprazolam in 2 and 24 of these cases, respectively. The results of this study provide a better understanding of the fentanyl epidemic in this region creating an opportunity to promote increased awareness, shift focus to harm reduction, and aid in minimizing public health risks.     

Seizures of Clandestinely Produced Tablets in Santa Catarina,Brazil: The Increase in NPS from 2011 to 2017

Ecstasy is the name given to a large group of substances known as “club drugs” traded in the form of tablets, powder and liquid that present a varied composition, including mainly 3,4-methylenedioxymethamphetamine (MDMA) and analogous substances, in addition to the growing presence of new psychoactive substances. Based on this, clandestinely produced tablets (“ecstasy tablets”) seized by police in Santa Catarina in the period from 2011 to 2017 were analyzed. During the study period, 3472 seizures occurred, which resulted in total 498,443 tablets seized. Seventy nine substances were identified. In the year 2011, about 90% of the tablets contained MDMA. This number decreased to 66.6% in 2017. On the other hand, there was an increase in the number of tablets that mainly contained synthetic cathinones, as well as tryptamine and piperazine derivatives. Police seizures in the metropolitan region of Florianópolis and on the coast prevailed over the rest of the state.     

Toxicological findings in Federal Aviation Administration general aviation accidents

Blood, urine, and tissue specimens were received from 377 Federal Aviation Administration (FAA) aviation fatalities during fiscal year 1989. Carbon monoxide at less than 10% saturation was found in 94% of the cases, and cyanide at less than 0.5 mg/L was found in 96% of the cases. Ethanol at greater than 10 mg/dL was found in 14.8% of the cases, but only 4.5% were determined to be due to ethanol ingestion from toxicological findings. Excluding nicotine and ethanol, 12.6% of the cases were positive for one or more drugs. Acetaminophen and salicylate were the most frequently found drugs. Cannabinoids were found in 1.3% of the cases and benzoylecgonine in 1.6%. There was minimal use of therapeutic drugs that cause central nervous system depression or stimulation. These results show no consistent pattern of drug involvement in civilian aviation fatalities.     

Toxicological investigations for drugs of abuse in arrested drivers: A 2-year retrospective study (2005–2006) in Strasbourg, France

Driving under the influence of drugs of abuse (DRUID) is prosecuted in France since 2001. Biological controls are performed according to a 2-step procedure: urine immunoscreening followed, in case of positivity, by a blood analysis using a separative technique coupled to mass spectrometry. This paper presents a 2-year (2005–2006) retrospective review of blood analyses performed in this framework at the Medico-Legal Institute of Strasbourg, France. Over this period 611 subjects were controlled on request of the authorities. Of this population, 532 (87.1%) were male. Mean age was 31.7 ± 14.4 years, 57.9% of subjects were in the range 15–29 and 31.1% in the range 20–24. On the 611 drivers, 296 (48.4%) were found positive for at least 1 drug using a preliminary blood immunoassay (ELISA). Among them, 254 were positive for cannabis, 81 for opiates, 22 for cocaine and 8 for amphetamine derivatives. Psychoactive medications were additionally tested in 278 drivers, and detected in 53 (19.1%). Benzodiazepines were the most frequently identified. On the 254 subjects tested positive for cannabis by ELISA, 202 had detectable levels of THC in blood (which is mandatory for engaging prosecution against the drivers). THC concentrations were in the range 0.1–49.9 ng/ml. Our results clearly illustrate the huge prominence of cannabis among substances involved in DRUID. This study also highlights some pitfalls of the DRUID repression policy currently followed by France, especially interpretation of low concentrations of drugs of abuse (in our study, 28.2% of drivers found positive for cannabis at the immunoassay screening had blood THC levels < 1 ng/ml): since no minimum threshold for blood concentrations has been defined in our country the fate of arrested drivers is prone to vary depending on the sensitivity of techniques employed from one laboratory to another, which might contradict the principle of equality of citizens before the law.     

Evaluation of cocaine, amphetamines and cannabis use in university students through hair analysis: preliminary results

The evaluation of drug abuse in a defined population was performed through toxicological hair analysis. Hair samples from university students ranging from 18 to 25 years of age were anonymously collected and screened for cocaine, amphetamines and cannabinoids by radioimmunoassay (RIA). Positive results (cut-off values adopted were 2 ng/mg for cocaine and amphetamines and 0.5 ng/mg for cannabinoids) were confirmed by GC/MS. Preliminary results showed 19% of positive results for cocaine on 200 samples analysed. No confirmed positive results were obtained for amphetamine analysis. RIA technique demonstrated its unsuitability for cannabinoids preliminary screening on hair, giving a high percent of false positive results.     

Concentrations of cocaine and its major metabolite benzoylecgonine in blood samples from apprehended drivers in Sweden

Cocaine and its major metabolite benzoylecgonine (BZE) were determined in blood samples from people arrested in Sweden for driving under the influence of drugs (DUID) over a 5-year period (2000-2004). Venous blood or urine if available, was subjected to a broad toxicological screening analysis for cannabis, cocaine metabolite, amphetamines, opiates and the major benzodiazepines. Verification and quantitative analysis of cocaine and BZE in blood was done by gas chromatography-mass spectrometry (GC-MS) at limits of quantitation (LOQ) of 0.02mg/L for both substances. Over the study period 26,567 blood samples were analyzed and cocaine and/or BZE were verified in 795 cases (3%). The motorists using cocaine were predominantly men (>96%) with an average age of 28.3+/-7.1 years (+/-standard deviation, S.D.). The concentration of cocaine was below LOQ in 574 cases although BZE was determined at mean, median and highest concentrations of 0.19mg/L, 0.12mg/L and 1.3mg/L, respectively. In 221 cases, cocaine and BZE were together in the blood samples at mean and (median) concentrations of 0.076mg/L (0.05mg/L) and 0.859mg/L (0.70mg/L), respectively. The concentrations of BZE were always higher than the parent drug; mean BZE/cocaine ratio 14.2 (median 10.9) range 1-55. Cocaine and BZE were the only psychoactive substances reported in N=61 cases at mean (median) and highest concentrations of 0.095 (0.07) and 0.5mg/L for cocaine and 1.01 (0.70) and 3.1mg/L for BZE. Typical signs of drug influence noted by the arresting police officers included bloodshot and glossy eyes, agitation, difficulty in sitting still and incoherent speech.