Fatal Poisoning Research Articles

A case of fatal poisoning caused by etomidate: evidence from pathological and toxicological analyses.

Etomidate is a nonbarbiturate sedative derived from imidazole. Prolonged and excessive use of etomidate can lead to the suppression of adrenocortical function, myoclonus, and even death. This report describes a rare case of a 47-year-old man who died from acute intoxication after oral ingestion of liquid containing etomidate. The cause of death was conclusively attributed to etomidate based on a comprehensive investigation, including autopsy, histopathological examination, toxicological analysis, and biochemical analysis. This is the first reported case of a fatality solely resulting from the oral ingestion of etomidate, which can provide valuable insights for future forensic investigations involving etomidate poisoning. Therefore, it is imperative to share this case with the scientific community.

A fatal case of desvenlafaxine and paroxetine poisoning

Desvenlafaxine (O-desmethylvenlafaxine) and paroxetine are antidepressants that inhibit serotonin reuptake. Despite their relatively safe profiles, several serious side effects, including serotonin syndrome, bleeding, mania, and high blood pressure, are observed. We report the confirmation of the death of a 41-year-old female, with an overdose of desvenlafaxine and paroxetine suspected as the main cause of death. To quantify the level of desvenlafaxine and paroxetine in whole blood and urine, solid phase extraction combined with liquid chromatography–tandem mass spectrometry was developed and validated. Calibration curves were linear with coefficients of determination (r2) >0.999 for desvenlafaxine and paroxetine. The limits of detection and the limits of quantification for both desvenlafaxine and paroxetine were 0.001 µg/mL and 0.02 µg/mL, respectively. Desvenlafaxine and paroxetine were detected in the postmortem samples, along with various psychiatric drugs, and the blood alcohol content level was below 0.010%. The concentrations of desvenlafaxine and paroxetine in the heart blood were 11.0 µg/mL and 2.1 µg/mL, respectively, indicating lethal concentrations. In the urine, the concentrations of desvenlafaxine and paroxetine were 87.7 µg/mL and 3.5 µg/mL, respectively. This is the first report to determine the blood concentration of desvenlafaxine in a fatal intoxication caused by an overdose of desvenlafaxine single formulation.

Fatal Intoxications with Zopiclone-A Cause for Concern?

Zopiclone, a controlled substance prescribed for insomnia, has become a common toxicological finding in forensic autopsy cases. This study investigated the role and extent of zopiclone use in fatal intoxications in Sweden. All forensic autopsy cases positive for zopiclone in femoral blood during 2012-2020 were selected. Among these cases, fatalities caused by intoxication according to the cause of death certificates issued by the forensic pathologist were identified. Intoxications where zopiclone contributed to the cause of death were included in the study. The Swedish Prescribed Drug Register was utilized to examine whether the included cases were prescribed zopiclone or not. In total 7320 fatal intoxications underwent a forensic autopsy during the study period, 573 of them were caused by zopiclone. Among the zopiclone fatalities, 87% (n = 494) had a prescription for zopiclone, and 8% (n = 43) were monointoxications. Most fatalities, 62% (n = 354) were suicides, and zopiclone was involved in about 17% (n = 354) of all intoxication suicides in Sweden. Women were significantly (p < 0.01) overrepresented in suicides with zopiclone, comprising 56% (n = 291) of fatalities. The median age was 55 years among zopiclone intoxications compared with 44 years amongst all fatal intoxications. This study demonstrates that the toxicity of zopiclone can be lethal both in combination with other substances and on its own. Most individuals dying in fatal zopiclone intoxications were prescribed zopiclone, which potentially indicates that a more restrictive prescribing rate could prevent future intoxication deaths, especially when caring for patients with an increased suicide risk.

Rapid determination of glyphosate and glufosinate in human blood by probe electrospray ionization tandem mass spectrometry

In forensic science, glyphosate (GLYP) and glufosinate (GLUF), a class of non-selective broad-spectrum herbicides, have been frequently encountered in many fatal poisoning and suicide cases due to their widespread availability. Therefore, it is essential to develop an effective method for detecting these compounds. Some conventional methods, such as gas chromatography–mass spectrometry (GC–MS) or liquid chromatography–mass spectrometry (LC–MS), have been reported to detect these compounds. However, these methods are not ideal for their time-consuming and non-sensitive feature. Herein, probe electrospray ionization (PESI) tandem mass spectrometry (MS/MS), a fast and sensitive technique, was applied for the determination of GLYP and GLUF in human blood, which can obtain analytical results within 0.5 min without derivatization and chromatographic separation. After protein precipitation of blood samples, the supernatant was mixed with isopropanol and ultra-pure water (1:1 v/v). Then, 8 μL of the mixture was introduced into the plastic sample plate for PESI-MS/MS analysis. The limits of detection (LODs) of the method were 0.50 μg/mL and 0.25 μg/mL for two analytes, and the limits of quantitation (LOQs) were both 1.00 μg/mL, which are higher than the concentration of reported poisoning and fatal cases. In the linear range of 1–500 μg/mL, the regression coefficients (r2) for GLYP and GLUF were over 0.99. The matrix effects ranged from 94.8 % to 119.5 %, and the biases were below 4.3 %. The recoveries ranged between 84.8 % and 107.4 %, and the biases were below 7.6 %. Meanwhile, the method was effectively utilized to detect and quantify the blood, urine, and other samples. Consequently, the results suggest that PESI-MS/MS is a straightforward, fast, and sensitive method for detecting GLUF and GLYP in forensics. In the future, PESI-MS/MS will become an indispensable technique for polar substances in grassroots units of public security where rapid detection is essential.

α-Pyrrolidinohexanophenone (α-PHP) and α-Pyrrolidinoisohexanophenone (α-PiHP): A Review.

New Psychoactive Substances are currently a serious and growing problem affecting public health worldwide. By 2022, 1184 of these substances had been identified over a period of 16 years. Within these, α-pyrrolidinohexanophenone (α-PHP) and α-pyrrolidinoisohexanophenone (α-PiHP) have emerged, two synthetic cathinones from the pyrovalerone derivates subgroup that are positional isomers of each other. Alpha-PHP appeared on the Japanese illicit drug market in 2014 and, two years later, α-PiHP was identified for the first time in China. They were placed in schedule II on the list of Psychotropic Substances under International Control in 2020 and in March 2023, respectively. Both cathinones have no therapeutic potential for medical use and therefore are abused for recreational habits, which can lead to fatalities. The most frequent adverse effects reported are cardiac, psychiatric, and neurologic, and fatal intoxications have already been described. In Portugal, their consumption and consequent seizures are more prevalent on the archipelagos, which has been aggravating the health situation. In conclusion, these types of substances are a challenge for forensic toxicology since they are easily synthesized, modified, and placed on the market. Therefore, more studies to develop analytical methods to detect them and more comprehensive legislation should be applied. Thus, this review aimed to address the legislative, physicochemical, toxicological, and analytical aspects of both substances.

Systematic Review of Fatal Sodium Nitrite Ingestion Cases: Toxicological and Forensic Implications.

Documented cases of sodium nitrite toxicity are almost exclusively caused by accidental ingestion; however, self-poisoning with sodium nitrite represents an increasing trend in nitrate-related deaths. This systematic review summarizes the most crucial evidence regarding the fatal toxicity of sodium nitrite. It identifies gaps and differences in the diagnostic forensic approaches and the detection methods of sodium nitrite intoxication. A total of eleven research articles were selected for qualitative and quantitative data. Most of the studies (6/11) were case reports. Fifty-three cases of fatal intoxication with sodium nitrite were chosen for the review. More research is required to develop cost-effective techniques and uniform cutoffs for blood nitrite and nitrate levels in the event of deadly sodium nitrite poisoning. There is still a lack of critical information on other matrices and the impact of time since death on toxicological results in such situations. The available evidence provides useful recommendations for forensic pathologists and health practitioners engaged in instances of sodium nitrite poisoning or death. The data should also set off alarm bells in the public health system, in prosecutor's offices, and for policymakers so that they may undertake preventative measures to stop and restrict the unregulated market for these substances.

Identification of lethal species in amanita section Phalloideae based on nucleotide signature and specific TaqMan-MGB probe and primer.

Amanita section Phalloideae consists of lethal toxic mushroom species, causing many fatal poisoning incidents worldwide. Molecular techniques of nucleotide signatures and single nucleotide polymorphism (SNP) detection could be used to develop a specific method for identifying lethal section (sect.) Phalloideae species. A comparison of 38 sequenced and 228 validated sequences from sect. Phalloideae species showed a 17-base pair nucleotide signature and an SNP site between the lethal and non-lethal species. A specific minor groove binder probe was designed based on them. The results indicated that this method exhibited excellent specificity for the lethal subgroup, good detection in samples subjected to simulated gastric digestion (60 min boiling and 120 min digestion), and a 10 pg./μL detection limit. This method enables accurate detection of target species in samples under complex conditions and can provide evidence for poisoning incidents caused by lethal sect. Phalloideae species to assist in targeted treatment strategies.

Exploring death scenes and circumstances in fatal opioid poisonings: Insights for preventive strategies using forensic autopsy cases in Western Denmark

IntroductionFatal opioid poisoning is a growing global issue. This study aims to describe circumstances surrounding fatal opioid poisonings by examining death scenes, demographics, and information from bystanders with the goal of informing prevention efforts. MethodsWe extracted data from the autopsy reports of 327 forensic autopsy cases with fatal poisoning involving methadone and/or morphine from 2013–2020. ResultsFatal opioid poisonings occurred in both rural and urban areas. Death scene was the decedent’s own home and a relative’s or friend’s home in 62% and 21%, respectively. The decedent died alone in 64% of the cases while other people were staying at the same address while death occurred in 30%. Decedents aged 15–34 years were more likely to die with other people staying at the same address than persons aged > 44 years (OR±SD: 2.3 ± 0.9, p = 0.005), and had lower postmortem blood methadone concentrations compared to persons > 34 years (Median [interquartile range]: 0.36 [0.23–0.62] vs 0.63 [0.28–1.2] mg/kg, p = 0.002). Female sex was more prevalent, and persons using illegal drugs were less prevalent in decedents aged > 44 years compared to those with age 15–44 years (29% vs 20%, p = 0.05% and 67% vs 89%, p < 0.001, respectively). Other psychoactive drugs were detected in 97% of decedents, mainly benzodiazepines (80%). ConclusionsPreventive strategies based on our findings include the need for harm reduction initiatives in both urban and rural areas, recognizing symptoms of fatal poisoning, and awareness of low tolerance among younger age groups. Urgent attention should be given to avoiding opioid use alone, particularly among older individuals, including women using prescribed opioids. Conveying the risks of polydrug use to all age groups is essential, especially co-use of sedative drugs.

Unraveling Hematotoxicity of α-Amanitin in Cultured Hematopoietic Cells.

Amanita phalloides poisonings account for the majority of fatal mushroom poisonings. Recently, we identified hematotoxicity as a relevant aspect of Amanita poisonings. In this study, we investigated the effects of the main toxins of Amanita phalloides, α- and β-amanitin, on hematopoietic cell viability in vitro. Hematopoietic cell lines were exposed to α-amanitin or β-amanitin for up to 72 h with or without the pan-caspase inhibitor Z-VAD(OH)-FMK, antidotes N-acetylcysteine, silibinin, and benzylpenicillin, and organic anion-transporting polypeptide 1B3 (OATP1B3) inhibitors rifampicin and cyclosporin. Cell viability was established by trypan blue exclusion, annexin V staining, and a MTS assay. Caspase-3/7 activity was determined with Caspase-Glo assay, and cleaved caspase-3 was quantified by Western analysis. Cell number and colony-forming units were quantified after exposure to α-amanitin in primary CD34+ hematopoietic stem cells. In all cell lines, α-amanitin concentration-dependently decreased viability and mitochondrial activity. β-Amanitin was less toxic, but still significantly reduced viability. α-Amanitin increased caspase-3/7 activity by 2.8-fold and cleaved caspase-3 by 2.3-fold. Z-VAD(OH)-FMK significantly reduced α-amanitin-induced toxicity. In CD34+ stem cells, α-amanitin decreased the number of colonies and cells. The antidotes and OATP1B3 inhibitors did not reverse α-amanitin-induced toxicity. In conclusion, α-amanitin induces apoptosis in hematopoietic cells via a caspase-dependent mechanism.

A fast and reliable LC-MS-MS method for the quantification of saxitoxin in blood plasma samples.

Saxitoxins (STXs) are potent neurotoxins produced by marine dinoflagellates or freshwater cyanobacteria known to cause acute and eventually fatal human intoxications, which are classified as paralytic shellfish poisonings (PSPs). Rapid analysis of STXs in blood plasma can be used for a timely diagnosis and confirmation of PSPs. We developed a fast and simple method of STX extraction based on plasma sample acidification and precipitation by acetonitrile, followed by quantification using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Our approach provides the results ≤30 min, with a limit of detection of 2.8 ng/mL and a lower limit of quantification of 5.0 ng/mL. Within-run and between-run precision experiments showed good reproducibility with ≤15% values. Standard curves for calibration were linear with correlation coefficients ≥0.98 across the assay calibration range (5-200 ng/mL). In an interlaboratory analytical exercise, the method was found to be 100% accurate in determining the presence or absence of STX in human plasma specimens, with recovery values of 86-99%. This simple method for STX determination in animal or human plasma can quickly and reliably diagnose STX exposures and confirm suspected PSP cases to facilitate patient treatment or expedite necessary public health or security actions.

Food-Borne Poisoning Accident from Amanitin Toxin in Wild Mushrooms - Xingtai City, Hebei Province, China, 2023.

Fatal poisonings caused by wild mushrooms containing amanita toxins pose a significant threat in the southern regions of China. These toxins primarily induce gastrointestinal symptoms initially, which are then followed by potentially life-threatening acute liver damage. This report contributes to the existing knowledge on these cases of poisoning by documenting the second occurrences in Hebei Province and the first occurrences in Xingtai City. Five individuals reported consuming wild mushrooms from the same origin, and laboratory tests confirmed the presence of α-amanitin in their blood samples. This underscores the risk associated with the collection and consumption of amanita toxin-containing mushrooms in Hebei. It is important to note that the identification of toxic and non-toxic mushrooms should not solely rely on personal experience or appearance.

Fatal poison in chicken meat. The death of Dmitry Shemyaka and the end of the Muscovite-Galician wars of the second quarter of the XV century

Fatal poison in chicken meat. The death of Dmitry Shemyaka and the end of the Muscovite-Galician wars of the second quarter of the XV century

Identification of post-mortem product of zolpidem degradation by hemoglobin via the Fenton reaction.

Zolpidem, N,N-dimethyl-2-[6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]acetamide, is a hypnotic agent widely used in clinical practice but is detected in many clinical cases of fatal intoxication and suicide. In forensic toxicology, the precise determination of zolpidem concentration in blood is a must to provide concrete evidence of death by zolpidem poisoning. However, the concentrations of zolpidem in blood at autopsy often differ from those at the estimated time of death. In the present study, we found that zolpidem was degraded by hemoglobin (Hb) via the Fenton reaction at various temperatures. The mechanism underlying zolpidem degradation involved the oxidation of its linker moiety. The MS and MS/MS spectra obtained by liquid chromatography quadrupole-Orbitrap mass spectrometry (LC-Q-Orbitrap-MS) showed the formation of 2-hydroxy-N,N-dimethyl-2-(6-methyl-2-(p-tolyl)imidazo[1,2-a]pyridin-3-yl)acetamide (2-OH ZOL) in Hb/H2O2 solution incubated with zolpidem and in the blood of several individuals who died from ingestion of zolpidem. These results suggest that 2-OH ZOL is the post-mortem product of zolpidem degradation by Hb via the Fenton reaction.

"Cosmetic" iatrogenic botulism : description of 2 cases in Switzerland

Botulism is a neuro-paralytic syndrome caused by the production of a neurotoxic protein by Clostridium botulinum. It is a rare but potentially fatal poisoning. Symptoms are due to blockage of neurotransmitter release at the neuromuscular junction. Botulism usually occurs following ingestion, inhalation or contact of the toxin with a wound. More recently, cases of iatrogenic botulism have been described, notably following the injection of toxin for therapeutic or cosmetic purposes. In spring 2023, an outbreak of iatrogenic botulism following intragastric injections was reported in Europe. Here, we provide an overview of botulism, followed by a presentation of the only two Swiss cases reported during the epidemic.

Carbon monoxide related deaths: A Verona case series. When cooperation becomes compulsory

IntroductionCarbon monoxide (CO) poisoning is a significant concern in forensic medicine, as it often presents unique challenges in terms of diagnosis, investigation, and determination of the cause of death. CO is a colourless, odourless, and tasteless gas that can be lethal when inhaled in high concentrations. It binds strongly to haemoglobin, forming carboxyhaemoglobin (COHb), which reduces the oxygen-carrying capacity of the blood, leading to tissue hypoxia and ultimately death. Materials and methodsCircumstantial data, medical history information, autopsy findings, and toxicological analysis results related to 24 CO poisoning cases at the Institute of Legal Medicine in Verona were collected and analysed. The data were examined in an integrated manner to identify correlations and common patterns. A comparison was also made with the data available in the literature. ResultsThe male gender was confirmed to be the most frequently involved. COHb levels were found to be less than 50% in 6 cases. Three individuals had concurrent cardiovascular pathologies, while 11 subjects tested positive for various substances, including alcohol, benzodiazepines, and morphine. In most cases, the manner of fatal intoxication was accidental, although 6 suicides and 1 homicide are reported. ConclusionsThe Verona case series demonstrates that deaths due to CO poisoning require a multidisciplinary approach. The integration of diverse expertise is essential for assessing the manner of death. This approach enables a comprehensive evaluation of the available data, aids in distinguishing between accidental, suicidal, and homicidal deaths, and ensures accurate and reliable forensic conclusions.

Accidental fatal poisoning in a child due to ingestion of Nerium oleander leaf.

Nerium oleander is an ornamental plant that belongs to the family Apocynaceae. It contains a cardiac glycoside named oleandrin, which is present in all parts of the oleander plant. Suicidal and medication-related deaths due to Nerium oleander poisoning are not uncommon. However, accidental deaths due to oleander leaf ingestion are most commonly encountered. We are reporting a case of an accidental ingestion of Nerium oleander leaf in a child by mistaking it for a guava leaf. The child presented to the casualty with vomiting, poor sensorium, hypotension, and shock. The child developed hyperkalemia, acute kidney injury, myocardial dysfunction, and bleeding manifestations. The urine output was decreased (< 0.5ml/kg/h). Later, the child died after 36h. On autopsy examination, periorbital puffiness and bluish discoloration of the nail beds were present. Petechial hemorrhages were present in the heart, kidney, and mesentery. The stomach mucosa was hemorrhagic. Histopathologically, the lung showed interstitial congestion, the liver showed centrilobular necrosis, and the kidney showed acute tubular necrosis. Toxicology analysis was positive for oleander poisoning. This case highlights the toxic nature of Nerium oleander ingestion and the importance of avoiding such plants around residential areas.

Opioid, cannabinoid, cocaine, and methamphetamine epidemics: History, risk factors associated with them, and characteristics of drug action

In the last century, mankind has made significant progress in the search and study of new pain-relieving drugs through the targeted synthesis of chemical analogs of natural opioids, cannabinoids, cocaine, and amphetamines. Experience with the medical use of new synthetic opioids, cannabinoids, and amphetamines has shown not only their high analgesic efficacy but also their high danger because of the risks of drug dependence and addiction, which have caused drug epidemics. The paper described the history of relevant drug epidemics, and the pharmacodynamics and pharmacokinetics of the most dangerous drugs, as well as the risks associated with drug epidemics, were outlined. Specifically, the risk of drug dependence to opioids, cannabinoids, amphetamine, and cocaine was not recognized until too late. Therefore, the drug crisis was initially largely iatrogenic. In recent decades, controls on the prescription of narcotic drugs have tightened; thus, drug addiction as iatrogeny occurs less frequently. However, criminal elements of society have established clandestine production of drugs and their realization in the youth and LGBT community disguising as new, fashionable designer drugs and devices for their use. Moreover, new synthetic drugs differ from natural drugs in their stronger psychostimulant effects, ability to cause addiction after the first use, and high risk of fatal poisoning. Thus far, no drugs were the treatment of opioid, cannabinoid, amphetamine, and cocaine abuse. However, the development of specific vaccines for these drugs has begun in recent years. Active immunization of drug abusers with specially created vaccines is expected to assist doctors in treating drug abusers in the future.

Quantitative analysis of phosphine in variety of biological samples from two cases of fatal poisoning

Quantitative analysis of phosphine in variety of biological samples from two cases of fatal poisoning

Receipt of opioid use disorder treatments prior to fatal overdoses and comparison to no treatment in Connecticut, 2016–17

ObjectiveTo determine the relative risk of death following exposure to treatments for OUD compared to no treatment. MethodsIn this retrospective cohort study we compiled and merged state agency data on accidental and undetermined opioid overdose deaths in 2017 and exposures to OUD treatment in the prior six months to determine incidence rates following exposure to different treatment modalities. These rates were compared to the estimated incidence among those exposed to no treatment to determine relative risk of death for each treatment exposure. ResultsIncidence rates for opioid poisoning deaths for those exposed to treatment ranged from 6.06±1.40 per 1000 persons exposed to methadone to 17.36±3.22 per 1000 persons exposed to any non-medication treatment. The estimated incidence rate for those not exposed to treatment was 9.80±0.72 per 1000 persons. With no exposure to treatment as referent, exposure to methadone or buprenorphine reduced the relative risk by 38% or 34%, respectively; the relative risk of non-medication treatments was equal to or worse than no exposure to treatment (RR = 1.27–1.77). Principal conclusionsExposure to non-MOUD treatments provided no protection against fatal opioid poisoning whereas the relative risk was reduced following exposures to MOUD treatment, even if treatment was not continued. Population level efforts to reduce opioid overdose deaths need to focus on expanding access to agonist-based MOUD treatments and are unlikely to succeed if access to non-MOUD treatments is made more available.

The stability of cyanide in human biological samples. A systematic review, meta-analysis and determination of cyanide (GC-QqQ-MS/MS) in an authentic casework 7 years after fatal intoxication

A 30 year old man was found with no signs of life in front of the house. The cyanide concentration in blood and urine was determined five years after the man’s death. What is more, a stability study was conducted for 730 days in an authentic casework blood sample. Sample preparation procedure included precipitation with methanol:water mixture, solid phase extraction (SPE) and derivatization with the use of PFB-Br (pentafluorobenzyl bromide). The sample was analyzed using GC-QqQ-MS/MS (gas chromatopraphy coupled with tandem mass spectrometry) isotope dilution method. Separation was done using a SH-RXI-5MS column (30 m x 0.25 mm, 0.25 µm). Detection of PFB-CN and PFB-13CN was achieved using a triple-quadrupole mass spectrometer with an electron ionization (EI) ion source in multiple reaction monitoring (MRM) mode. After 5 years from the man’s death, cyanide concentration was: 1900 ng/mL in blood and 500 ng/mL in urine. Stability study performed in an authentic blood sample 6 and 7 years after the man’s death revealed cyanide concentrations of 1898.2 ng/mL and 1618.7 ng/mL, respectively. While spectrophotometric and colorimetric methods recorded both decrease and increase in cyanide concentration over time, newer chromatographic methods mainly indicate a decrease. The studies presented in this paper seem to confirm this trend. However, in order to interpretate the results of cyanide concentration in biological material reliably, more research is still necessary.