Post-mortem cases involving amphetamine-based drugs in the Netherlands: Comparison with driving under the influence cases

In this study we reviewed the post-mortem cases in the years 1999–2004 that were presented at the Netherlands Forensic Institute. The concentrations of amphetamine-based drugs in femoral blood from cases of suspected unnatural death were compared with concentrations in whole blood from non-fatal cases of driving under the influence (DUI cases) and with literature. Furthermore, the combinations with other drugs and/or alcohol were investigated. Amphetamine-based drugs were present in 70 post-mortem cases and 467 DUI cases. The most detected amphetamine-based drug was MDMA, followed by amphetamine. The presence of MDA could usually be explained by metabolism of MDMA. Methamphetamine and MDEA were rarely present. Frequently, the amphetamine-based drugs were taken in combination with alcohol and/or other non-amphetamine-based drugs such as cocaine or cannabinoids. The 70 post-mortem cases were divided into 38 amphetamine-based drug caused (i.e. the amphetamine-based drug directly caused or contributed to the death) and 32 amphetamine-based drug related deaths (i.e. death was not directly caused by the amphetamine-based drug). In the latter category, other (poly)drug intoxications and death by violence or drowning were the most frequent causes of death.In 30 cases, MDMA caused death directly. The range in blood concentrations of MDMA in these cases was substantial, i.e. 0.41–84 mg/L with a median concentration of 3.7 mg/L (n = 30). MDMA blood concentrations in the MDMA related deaths (n = 20) and in the DUI cases (n = 360) varied up to 3.7 and 4.0 mg/L, respectively. Seven victims died from the direct effects of amphetamine; the blood concentration of amphetamine ranged from 0.24 to 11.3 mg/L, with a median concentration of 1.7 mg/L (n = 7). The median concentrations of amphetamine in the amphetamine related deaths (n = 13) and the DUI cases (n = 208) were much lower, i.e. 0.28 and 0.22 mg/L, respectively. Amphetamine blood concentrations up to 6.0 and 2.3 mg/L were seen in the drug related deaths and DUI cases, respectively. The most frequently encountered amphetamine-based drugs in the investigated deaths were MDMA and amphetamine. The majority of MDMA- and amphetamine-caused deaths, i.e. 90% of these deaths, occurred with blood concentrations above 1.5 and 0.80 mg/L, respectively. MDMA and amphetamine blood concentrations in drug related deaths and DUI cases, however, overlap the range of fatal concentrations. Therefore, MDMA or amphetamine concentrations should never be used alone to establish the cause of death.     

Increasing Methamphetamine Detection in Cases of Early Childhood Fatalities

Age and organ maturity can influence drug toxicity in children; however, most clinical data and literature are based on drug concentrations in adults. Therefore, the interpretation of drugs detected in children is often difficult or not possible. Retrospective reviewing of pathology and toxicology information from postmortem cases may assist in future interpretations or identify drug trends. A search of the Forensic Science SA case files was undertaken over 15 years from January 2002 to December 2016 for all children (<13 years). Of the 412 pediatric coronial cases, toxicological information was available on 373. At least one drug was detected in 94 cases with paracetamol, ibuprofen, codeine and hospital-administrated lignocaine and morphine among the most commonly detected agents. Methamphetamine, one of the most commonly abused illicit drugs in Australia, was found in seven cases. In the methamphetamine cases, deaths were associated with shared sleeping in three, pneumonia in one, and stillbirth in one. Methamphetamine was considered potentially contributory to death in two cases. The causes of death in the remaining two cases were undetermined. As six of the seven positive cases occurred in the 2012–2016 (n = 106) timeframe, an increase has occurred over recent years in the number of infants and young children presenting to forensic autopsy in South Australia who have detectable concentrations of methamphetamine. If this is an indication of a more generalized increased childhood exposure in the community there may be significant long-term physical and psychological effects.     

完善我国药品不良反应救济机制的法律思考

药品不良反应是在正常使用合格药品时产生的有害或意外反应。因药品不良反应导致患者严重损害的,相关主体应对受害人进行赔偿。在我国现行法下,药品不良反应法律责任不同于医疗事故责任、产品责任和国家赔偿责任,而属于侵权法中的公平责任。我国应及早建立和完善药品不良反应救济机制,实行药品不良反应救济基金制度。     

药物不良事件及其法医学鉴定

目的研究药物不良事件的法医学鉴定原则及注意事项,为此类案件的法医学鉴定提供参考并积累基础资料。方法通过对33例药物不良事件法医学鉴定案件的回顾性分析,总结药物不良事件相关案件的法医学鉴定原则及注意事项。结果药物不良事件的法医学鉴定案件有增长趋势,患者以女性多见(20例,60.6%)。33例药物不良事件中,以医疗过错鉴定案件多见(21例,63.6%),21例医疗过错鉴定案件中,只有1例(4.8%)与医院过量使用药物有关,其他均未发现医院存在医疗过错;非法行医案8例(24.2%),均与使用药物不当有关。法医鉴定类型以活体鉴定为主(27例,81.8%),死亡案件6例(18.2%)。结论药物不良事件的法医学鉴定案例在不断增加并具有自身特点和复杂性,应引起鉴定人的重视。     

"Magical thinking," suicide, and malpractice litigation

Prospective clinical assessment of suicidality differs significantly from that used retrospectively in malpractice litigation. In the latter context, the judge or jury may be susceptible to hindsight reasoning and a disproportionate emphasis on the specific method of suicide, exaggerating its foreseeability and "magically" linking the means of death to the treating clinician, especially in the case of suicide by an overdose of prescribed medication. Such magical thinking, moreover, is rooted in the clinical context of suicide: The errors of reasoning observed in the courtroom exhibit striking parallels with the mind-set of the suicidal patient. An understanding of these dynamics suggests appropriate precautions for the clinician and thus contributes to the prevention both of suicide and of malpractice litigation.     

idPAD: Paper Analytical Device for Presumptive Identification of Illicit Drugs

As drug overdose deaths across the United States continue to rise, there is increasing interest in field testing of illicit substances. This work discusses a paper-based analytical device (idPAD) that can run a library of 12 colorimetric tests at the same time, each detecting different chemical functional groups and materials found in illicit drugs, distractor substances, and cutting agents. The idPAD requires no electricity, costs less than $2 USD, and requires minimal training to operate. The results of the 12 tests form a color barcode which is “read” by comparison to standard images. The accuracy of the idPAD was assessed using samples of heroin, cocaine HCl, crack, and methamphetamine at concentrations of 25%–100% in a lactose matrix, as well as pure lactose. Based on 840 “reads” by three different users, the idPAD showed 95% sensitivity and 100% specificity for detecting these drugs; the most common error was mistaking cocaine HCl for crack or crack for cocaine HCl. In a second step, samples of heroin, cocaine, and methamphetamine (n = 30) and distractor substances (pharmaceuticals, cutting agents, and other illicit drugs, n = 64) were tested by two readers, yielding a sensitivity of 100% and specificity of 97%. Targeted substances were detected reliably at 55–180 μg/lane, and the idPAD was found to be stable for at least 3 months when stored at room temperature. The library approach used in the idPAD may provide the accuracy and robustness necessary for a presumptive field drug test.     

Undetermined Manner of Death: An Autopsy Series

A manner of death may be ruled undetermined by the forensic pathologist when there is insufficient information about the circumstances surrounding the death to make a ruling. The aim of our study was to retrospectively analyze a series of autopsy cases that were classified as undetermined manner of death after complete investigations. In all, 48 cases were examined. In 23 cases (48%), the cause of death was determined. The most frequent cause of death was toxic death (n = 11). More than one manner of death was deemed conceivable for most cases (n = 39). The most frequent and the most probable manner of death was accident (n = 37). Homicide was not excluded in about 23% of the cases. Our study showed that the manner of death may remain undetermined despite an established cause of death, and even when two or more conceivable causes of death are considered. Our study pointed out that undetermined manner of death covers a wide range of situations and that homicide may be underestimated.     

An Unusually High Cocaine Blood Concentration in an Impaired Driving Investigation

Cocaine is an illicit drug frequently encountered by forensic practitioners in driving under the influence of drugs (DUID) casework. Whole blood collected from a suspected drugged driver was found to contain 3.000 mg/L cocaine, 1.600 mg/L benzoylecgonine, and 0.260 mg/L methamphetamine. The high concentration of cocaine, while common in overdose death investigations, is unusual for an impaired driving case. Information from the officer revealed that the motorist swallowed cocaine during the traffic stop. Although a cocaine DUID charge could not be pursued, the blood methamphetamine concentration exceeded the State of Nevada “per se” limit for operating a motor vehicle. The motorist was successfully prosecuted for DUID based on his admission of using methamphetamine prior to driving and the blood methamphetamine result. This case highlights the importance of considering case history when interpreting laboratory results and the application of jurisdictional statutes as an approach to prosecuting suspected drug‐impaired drivers.     

FORENSIC Autopsy of People Having Committed Suicide in 2002 and in 2012: Comparison of Epidemiological and Sociological Data

This work compares epidemiological and sociological data on persons having committed suicide in 2002 and in 2012 through a retrospective study of every suicide case having led to an autopsy at the Institute for Forensic Medicine of Lyon in 2002 and in 2012. The study included sociodemographic data, medical data, and toxicological data. A total of 486 cases were included (242 cases in 2002 and 244 cases in 2012). People committing suicide were on average older in 2012 than in 2002 with a larger proportion of over 55. There was also an increase in the proportion of psychiatric antecedents (p < 0.001). Whatever the date of death by suicide, the most affected age range is the 45–54. The results highlight the necessity of bolstering the prevention plans, in particular for people over 45.     

Drug levels found in cases of fatal self-poisoning

A list of drug levels found in cases of fatal self-poisoning is presented here. These are all cases where only one drug was found and the cause of death in each case was attributed to an overdose of that particular drug. For each case a full drug screen was carried out. In general thin-layer chromatography (TLC) was used as the initial screening technique and any positive findings were then confirmed by gas liquid chromatography (GLC) and high performance liquid chromatography (HPLC). When the drug had been positively identified, the blood level was measured.     

Medical examiner response to the drug overdose epidemic in King County Washington: “Real-time” surveillance,data science,and applied forensic epidemiology

As the overdose epidemic overwhelmed medicolegal death investigation offices and toxicology laboratories, the King County Medical Examiner's Office responded with “real-time” fatal overdose surveillance to expedite death certification and information dissemination through assembling a team including a dedicated medicolegal death investigator, an information coordinator, and student interns. In-house testing of blood, urine, and drug evidence from scenes was performed using equipment and supplies purchased for surveillance. Collaboration with state laboratories allowed validation. Applied forensic epidemiology accelerated data dissemination. From 2010 to 2022, the epidemic claimed 5815 lives in King County; the last 4 years accounted for 47% of those deaths. After initiating the surveillance project, in-house testing was performed on blood from 2836 decedents, urine from 2807, and 4238 drug evidence items from 1775 death scenes. Time to complete death certificates decreased from weeks to months to hours to days. Overdose-specific information was distributed weekly to a network of law enforcement and public health agencies. As the surveillance project tracked the epidemic, fentanyl and methamphetamine became dominant and were associated with other indicators of social deterioration. In 2022, fentanyl was involved in 68% of 1021 overdose deaths. Homeless deaths increased sixfold; in 2022, 67% of 311 homeless deaths were due to overdose; fentanyl was involved in 49% and methamphetamine in 44%. Homicides increased 250%; in 2021, methamphetamine was positive in 35% of 149 homicides. The results are relevant to the value of rapid surveillance, its impact on standard operations, selection of cases requiring autopsy, and collaboration with other agencies in overdose prevention.     

Postmortem forensic toxicology of trazodone

Trazodone is a popular antidepressant medication that has been available for approximately 30 years. It has a reputation as a safe drug with relatively few reported fatalities attributed solely to it. We review the pharmacology and forensic toxicology of trazodone and report toxicology and cause and manner of death in a series of 37 deaths in which trazodone was detected. Although the normal upper therapeutic blood concentration for trazodone is about 2 mg/L, fatalities are rarely attributed solely to it at blood concentrations below 9 mg/L. Considering the pharmacology of the drug, potential interactions between other drugs with serotonin reuptake properties need to be considered, as does the increased susceptibility to the toxic effects in patients with pre-existing heart disease. In the cases reviewed, none were attributed solely to trazodone, although trazodone was frequently present together with other serotonergic drugs, such as the selective serotonin reuptake inhibitors like fluoxetine and sertraline. Ten cases had blood trazodone concentrations above 2 mg/L. Of these cases, trazodone played a primary role in the death of three subjects, with blood concentrations all greater than 9 mg/L. We confirm the conclusions of others that trazodone is a relatively safe drug except in massive overdose, although its toxicity may be influenced by the presence of other drugs and underlying pathophysiology.     

心外科手术后死亡医疗纠纷尸检分析

目的从尸检角度讨论心外科手术后死亡的死因及诊疗缺陷。方法按临床诊断、手术类型、死亡时间、死亡特点、尸检特点、纠纷特点、诊疗缺陷等方面,比较所选案例的临床、尸检资料特点。结果心瓣膜置换手术4例,冠心病冠脉搭桥手术1例,先心病大动脉转位手术1例。心肌梗死2例,心肌广泛损伤1例。心内膜感染2例,多器官功能衰竭1例。家属怀疑诊疗不当6例。诊疗缺陷主要为手术适应证、手术时机,手术器材的选用,手术操作,术后病情观察、处理不及时,对病情严重程度、手术风险及预后的告知不充分。结论尸检不仅能查明死因,还可帮助评价手术质量、术后处理的诊疗质量,对解决纠纷具有重要的辅助作用。     

Post-mortem investigation of calcium content in liver, heart, and skeletal muscle in accidental hypothermia cases

The identification of hypothermia as cause of the death was always quite problematic in the field of forensic medicine. The aim of the present study was to verify the determination of calcium content in post-mortem liver, heart, and skeletal muscle samples as the biochemical marker defining hypothermia as the cause of death. The study involved 43 autopsy cases in which the circumstances of death indicated the effects of overcooling. The control group consisted of material collected from the corpses of 30 persons who were not exposed to low temperatures but died due to technical injuries (n = 5), asphyxia (n = 6), intoxication with ethanol and other substances (n = 8), and acute myocardial infarction/ischemia (n = 11). The concentration of calcium in autopsy samples was determined applying flame atomic absorption spectroscopy. Our study showed no significant differences of calcium content in tissues of persons who died due to hypothermia, over those who died in normothermic conditions.     

Analysis of 2,4-Dinitrophenol in Postmortem Blood and Urine by Gas Chromatography–Mass Spectrometry: Method Development and Validation and Report of Three Fatalities in the United States

2,4-dinitrophenol (2,4-DNP) is a compound used in the early 1900s as a weight-loss drug but later prohibited due to its severe adverse effects, including death. It has however been attracting interest, due to its weight-loss properties, and appears to be re-emerging in forensic casework. As 2,4-DNP is available for use in industry and as a pesticide and easily accessible online, the dissemination of this drug can be fast. The compound exerts its effects through inhibition of ATP synthesis, and corresponding thermogenic energy loss which can be fatal. A method for qualitative and quantitative analysis of 2,4-DNP in blood and urine specimens using GC-MS with hydrogen as carrier gas is described. The method was validated and displayed acceptable performance parameters with linearity (R² higher than 0.998), inter-assay imprecision (lower than 10.6%), intra-assay imprecision (lower than 10.7%), and extraction efficiency (92.1%). Stability of 2,4-DNP in blood and urine was studied, and the drug was stable up to 30 days refrigeration or frozen. Six cases in United States suspected to be related to 2,4-DNP were analyzed. Three cases were found to be positive for 2,4-DNP. Concentrations of 2,4-DNP were in the range of 61.6–220 mg/L in urine and <3–114 mg/L in blood. Based on our findings, we suggest that medical examiners and forensic toxicologists be aware of the reappearance of 2,4-DNP, including this compound as a target in death investigations related to weight-loss drugs.     

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.