Fulminant liver failure in a young child following repeated acetaminophen overdosing

Acetaminophen (paracetamol), a widely used analgetic drug, is well tolerated at therapeutic doses, but may cause severe hepatotoxicity when ingested in large overdose. Self-poisoning is still very popular in adults and accidental ingestion of one single overdose occurs occasionally in children. In contrast, lethal intoxication in children after repeated administration of therapeutic doses is a very rare event. This case report describes an iatrogenic acetaminophen overdosing in a 5-year-old child receiving 8.5 g acetaminophen in 48 h. Fulminant liver failure developed within 60 h. Autopsy findings included panlobular liver cell necrosis. Acetaminophen serum levels were rather low compared to cases with ingestion of one single overdose. Postmortem diagnosis of chronic acetaminophen intoxication as cause of death should include the clinical history as well as, if available, the calculated drug serum half-life.     

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.     

Suicide via insulin overdose in nondiabetics: the New Mexico experience

Four cases of self-injected insulin overdose in nondiabetic individuals are presented. Included are two cases of presumed insulin overdose (no autopsy), one case with elevated vitreous insulin (autopsy), and one case with elevated postmortem blood insulin and low blood C peptide (autopsy). These cases demonstrate the need for a thorough scene investigation, complete autopsy, and proper collection and storage of specimens to certify a death caused by insulin intoxication as well as to determine the manner of death. Appropriate collection and preservation of postmortem blood samples are discussed.     

Clinical effects and lethal and forensic aspects of propofol

Propofol is a potent intravenous anesthetic agent that rapidly induces sedation and unconsciousness. The potential for propofol dependency, recreational use, and abuse has only recently been recognized, and several cases of accidental overdose and suicide have emerged. In addition, the first documented case of murder using propofol was reported a few months ago, and a high profile case of suspected homicide with propofol is currently under investigation. A number of analytical methods have been employed to detect and quantify propofol concentrations in biological specimens. The reported propofol-related deaths and postmortem blood and tissue levels are reviewed. Importantly, limitations of propofol detection are discussed, and future considerations are presented. Because propofol has the potential for diversion with lethal consequences, the forensic scientist must have a basic understanding of its clinical indications and uses, pharmacologic properties, and detection methods. In addition, medical institutions should develop systems to prevent and detect diversion of this potential drug of abuse.     

Amitriptyline abuse and misuse

Deaths related to amitriptyline toxicity are relatively common and are typically related to suicidal overdose. A less well-recognized situation of amitriptyline intoxication occurs when the drug is abused for its euphorigenic effects. An amitriptyline-related death due to a mixed drug intoxication is presented. Death investigation revealed that the death was accidental rather than suicidal. The case serves to remind forensic investigators that not all amitriptyline overdose deaths represent suicides. A segment of the population is known to abuse amitriptyline.     

Prevalence of xylazine in overdose cases: An analysis of Miami-Dade County medical examiner case data

Xylazine sedative, muscle relaxant, and analgesic used in a veterinary setting. Although xylazine was never approved for therapeutic use in humans, it has become popular in the street drug market as a cutting or bulking agent in the fentanyl and heroin supply. Recently, there has been a significant increase in the detection of xylazine in postmortem forensic toxicology casework. Xylazine can be identified during routine toxicology screening utilizing instrumentation such as gas chromatography–mass spectrometry and liquid chromatography–mass spectrometry. Using the Miami-Dade Medical Examiner's LIMS system, all cases received between 2015 and 2022 in which xylazine was reported were reviewed. The cases studied include accidental drug overdose deaths in Miami-Dade County as well as Collier County (Naples), Florida. In total, there are 170 cases; the majority are accidental polydrug overdoses involving White males between the ages of 25 and 44 years old. Of the 170 cases, 37% listed xylazine as the cause of death. 13% of cases contained only xylazine and fentanyl while the remaining 87% of deaths were attributed to polydrug toxicity involving two or more substances. The prevalence of xylazine can be attributed to its increasing popularity rather than an increase in caseload. In 2019, xylazine was present in only 4% of all accidental fentanyl overdoses. By 2021, this percentage has increased sixfold, with xylazine present in 24% of all accidental fentanyl overdoses. Despite a decrease in fentanyl overdoses in 2022, the percentage of xylazine detection remained the same.     

胰岛素中毒法医学研究进展

胰岛素作为一种临床上常见的降血糖药物,可以有效控制糖尿病患者血糖,使之维持在正常范围。但过量胰岛素可导致死亡,其中以意外中毒最多见,其次为自杀,胰岛素他杀虽极为罕见,但值得高度重视。胰岛素中毒致死的法医学鉴定极为困难,虽然相关研究已取得一定的进展,但在法医学实践中,这类案件仍然是一大难题。本文从法医病理学的角度,对胰岛素中毒的死亡机制、病理学改变、检测手段、注意要点及诊断要点进行综述,为法医学实践提供帮助。     

Fatal Insulin Overdoses: Case Report and Update on Testing Methodology

Suicidal insulin overdoses are an under‐recognized and uncommon cause of death, often relying on scene and nonspecific autopsy findings. Here, we present a case report of a fatal exogenous insulin overdose in a patient with type 1 diabetes. In our case, there were no contributory autopsy findings; however, serum analog aspart insulin levels were c. 10× the predicted therapeutic upper limit (4000, reference 6.6–55 uU/mL), which correlated with scene findings. This was specifically determined by a newly developed immunocapture liquid chromatography–tandem mass spectrometry assay, able to discriminate between various synthetic insulin analogs. Total insulin levels by immunoassay were highly elevated on the Siemens Advia Centaur, but not the Roche platforms (4741 vs. 5.2 uU/mL, respectively), showing variable sensitivity of detection within the same analog depending on assay. We discuss the prevalence and features to look for at autopsy in these types of cases. Additionally, analytical options for testing insulin levels, including new methodologies, guidance on collection of samples, as well as an outline of available historical reference range data are discussed.     

Digoxin-like immunoreactive substance in postmortem blood of infants and children

A digoxin-like immunoreactive substance (DLIS) has been reported in the serum of infants not receiving digoxin. This study was undertaken to determine if DLIS is present in the postmortem blood and tissues of infants or children and whether the endogenous substance could interfere with forensic toxicological analysis in suspected overdose. Ninety blood specimens taken from the heart at autopsy of children or infants were screened for DLIS using commercial radioimmunoassay kits. The average age at death in these cases was 8.6 months, the median age was 2 months. DLIS equivalent to 0.25 to 2.0 ng/mL digoxin was found in one third of the cases. The incidence of positive findings was 5/6 stillborns, 10/45 Sudden Infant Death Syndrome (SIDS), 10/15 deaths as a result of infection, 4/7 homicides, 1/8 deaths caused by congenital defects, and 0/9 accidental deaths. The body distribution of DLIS was investigated and highest levels were found in the liver. Findings of DLIS in blood were correlated with renal failure, (elevated vitreous urea nitrogen), electrolyte imbalance, and liver trauma. Apparent concentrations were in the equivalent therapeutic range of digoxin and would not be confused with accidental or intentional overdose with digoxin.     

Fentanyl concentrations in 23 postmortem cases from the hennepin county medical examiner's office

The purpose of this study was to compare blood fentanyl concentrations in fentanyl-related deaths with fentanyl concentrations found incidentally at autopsy, as well as with fentanyl concentrations found in hospitalized patients receiving fentanyl. Between the years 1997 to 2005, 23 fentanyl-positive postmortem cases were identified. Nineteen of 23 (82.6%) cases were deemed to be drug overdoses. Fentanyl alone was responsible for 8 of the 19 (42.1%) overdose deaths. Mean and median fentanyl concentrations were 36 (SD 38) microg/L and 22 microg/L, respectively, range 5-120 microg/L. Seven of the cases were accidental, one undetermined. The remaining 11 of the 19 (57.9%) cases were mixed drug overdoses. Fentanyl concentrations in these cases were 31 (SD 46) microg/L, range 5-152 microg/L. All of the mixed drug overdoses were determined to be accidental. Four cases where fentanyl was considered an incidental postmortem finding were determined to be natural deaths. In hospitalized inpatients (n = 11) receiving fentanyl 2 of the patients receiving fentanyl for chronic pain for more than 3 months had concentrations of 8.5 microg/L and 9.9 microg/L. The other nine inpatient concentrations were less than 4 microg/L. In conclusion, blood fentanyl concentrations found in cases where fentanyl alone was determined to be the cause of death were similar to cases where fentanyl was part of a mixed drug overdose. There was also considerable overlap between fentanyl concentrations in fentanyl-related overdose deaths compared to hospitalized patients being treated for chronic pain. Fentanyl concentrations in postmortem cases must be interpreted in the context of the deceased's past medical history and autopsy findings.     

Complex autoerotic death with full body wrapping in a plastic body bag

Autoerotic deaths are normally classified as accidental deaths occurring during individual, and usually solitary, sexual activity in which a device, apparatus, or prop used to enhance sexual stimulation of the deceased somehow causes unintended death. The most common methods of autoerotic practices are asphyxia by hanging, ligature, plastic bag, chemical substances, or a mixture of these. However, atypical methods such as overdressing/body wrapping have also been reported. In fact, overdressing/body wrapping is so rare that it is implicated in only 1.5% of published cases. Although plastic bags are often implicated in autoerotic deaths, there has been only one previous case that involved a plastic covering the victim's body from head to toe. We here report the case of a 34-year-old man who died due to asphyxia, secondary to body wrapping in the largest and most complex plastic bag ever involved in a published case of autoerotic death.     

Intentional overdose of glargine insulin: Determination of the parent compound in postmortem blood by LC-HRMS

Insulin glargine is a long-acting insulin analog that is converted after enzymatic cleavage of the arginine pair of the β-chain into its main metabolite M1 (21^A-Gly-insulin), which is responsible for the hypoglycemic activity. In all the overdose cases described in the literature, only M1 concentrations have been reported, whereas insulin glargine was always absent or below the limit of quantitation. In this study, we present a case of suicide of a young nurse by injection of insulin glargine in which the parent molecule was found at a toxic concentration in blood. The determination and the discrimination of insulin glargine from human insulin and other synthetic analogs in the blood specimen were performed by liquid chromatography coupled to high-resolution mass spectrometry (Waters XEVO G2-XS QToF) and extraction after precipitation in the presence of bovine insulin (internal standard), with a mixture of acetonitrile/methanol +1% formic acid followed by purification on solid phase extraction cartridges C18. Glargine insulin tested highly positive in the blood with a concentration of 1.06 mg/L. Due to the difficulty in obtaining a M1 pure standard, the metabolite could not be dosed. This unique presence of the parent molecule, reported for the first time, can be explained by inter-individual variability in the rate of conversion to metabolite. Intravenous injection versus subcutaneous injection can also explain the presence of insulin glargine. Finally, the dose injected may have been so high that saturation of the proteolytic enzymes responsible for conversion to M1 should have occurred.     

Delayed elimination in humans after ingestion of colchicine: Two fatal cases of colchicine poisoning

Colchicine has been widely used in the treatment of acute gout over the years, but it has a narrow therapeutic index, and overdose can be life threatening. A method using ultra-high-performance liquid chromatography–tandem mass spectrometry system was applied in two fatal cases of colchicine poisoning in this study to the determination of colchicine in blood. In case 1, a 19-year-old man suffered from depression and ingested 160 colchicine tablets (each 0.5 mg). The concentration of colchicine in his blood samples showed a fluctuating trend and kept above the therapeutic steady-state concentration for 5 days. In case 2, a 70-year-old female patient with a history of gout and chronic colchicine intake ingested five times the usual dose of colchicine (5 mg) and died after 12 days of medical care, with 5 ng/mL of colchicine in her blood sample. Our findings suggest that the delayed elimination and accumulation in humans after colchicine overdose could keep the concentration of colchicine maintaining above the therapeutic steady-state concentration for many days before dying, probably along with a fluctuating trend.     

The acetaminophen experience in south Florida

Toxicology records of the Dade County Medical Examiner Department were reviewed for the years 1972 to 1981. Any case in which acetaminophen was detected, regardless of the cause of death, was included in the study. Of 95 cases where acetaminophen was detected, no trends were observable in age, sex, or race. Acetaminophen deaths have increased in recent years, probably because of increased marketing of products containing this substance. Some two thirds of the cases involved suicides or accidental deaths, with 40 cases being directly attributable to overdose with a variety of drugs. It is suggested that acetaminophen may be a useful indicator of polydrug overdoses.     

Our experiences with fatal ecstasy abuse (two case reports)

Ecstasy is a psychostimulative drug (ab)used mostly by teenagers and young adults in discotheques and on the “rave” parties. Older adults ecstasy abusing cases are very rare. Among four cases of ecstasy abuse with fatal outcome noticed and examined in Slovenia, two were examined at our Institute of Forensic Medicine in Ljubljana. The first case was the accidental intoxication with 3,4 methylenedioxymethamphetamine (MDMA) on “rave” party, the second case was suicidal intoxication with combination of insulin and MDMA. Because of the increasing popularity of MDMA, it is important for all emergency physicians to be well educated in prompt recognition of MDMA intoxication symptoms. It is important that emergency physician carefully examines the death scene.     

Plastic bag asphyxia in southeast Scotland

Death resulting from plastic bag asphyxia has been recognized for >40 years, but relatively little is known about either its epidemiology or its pathophysiology. Over 15 years (1984-1998), 30 deaths were attributed to plastic bag asphyxia among the 14,560 autopsies performed in the Forensic Medicine Unit in Edinburgh. These 30 deaths involved 20 male and 10 female subjects, with an age range of 13 to 81 years. Eleven had some alcohol measurable in the blood, with four having levels >80 mg/dl. Only one individual appeared to have ingested a drug overdose, but inhaled substances within the plastic bag may have contributed to death in five cases. The absence of childhood accidental deaths may reflect successful preventive measures. The 3 accidental deaths involved adults (including 2 who died of autoerotic asphyxia), and the remaining deaths were 27 suicides. Of those who committed suicide, most (59%) had chronic psychiatric illness rather than chronic debilitating or terminal physical illness. In contrast with reports from the United States, publicity associated with "self-deliverance" did not result in an increased number of deaths from plastic bag asphyxia (4 deaths in this series). Analysis of the circumstances of all the deaths revealed them to be difficult to predict and hence prevent.     

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.     

Field-portable detection of fentanyl and its analogs: A review

The need to detect fentanyl and its analogs in the field is an important capability to help prevent unintentional exposure or overdose on these substances, which may result in death. Many portable methods historically used in the field by first responders and other field users to detect and identify other chemical substances, such as hazardous materials, have been applied to the detection and identification of these synthetic opioids. This paper describes field portable spectroscopic methods used for the detection and identification of fentanyl and its analogs. The methods described are automated colorimetric tests including lateral flow assays; vibrational spectroscopy (mid-infrared and Raman); gas chromatography–mass spectrometry; ion mobility spectrometry, and high-pressure mass spectrometry. In each case the background and key details of these technologies are outlined, followed by a discussion of the application of the technology in the field. Attention is paid to the analysis of complex mixtures and limits of detection, including the required spectral databases and algorithms used to interrogate these types of samples. There is also an emphasis on providing actionable information to the (likely) non-scientist operators of these instruments in the field.     

Verapamil toxicity: an unusual case report and review of the literature

Verapamil blocks the rapid influx of calcium into the cardiac myocytes of the cardiac conduction system and smooth muscle of the vasculature, resulting in decreased myocardial contractility, prolonged conduction time, and vascular relaxation. A sustained-release form, verapamil SR (or ER), is available that contains higher levels of medication and requires only once-daily dosing. The majority of reported fatal cases of verapamil toxicity are due to massive, intentional overdoses. Herein, we present an unusual case of fatal verapamil SR toxicity in a 57-year-old female that resulted from accidental overdose of only 3 tablets (720 mg), as witnessed by the decedent's daughter. In spite of the low dose ingested, the postmortem cardiac blood verapamil level was clearly toxic (6000 ng/mL, or 6 mg/L). Her preexisting medical conditions included hypercholesterolemia, hypertension, iron deficiency anemia, diabetes mellitus, and associated mild chronic renal failure. Complicating factors, which likely include the decedent's preexisting renal and cardiac disease, and a review of the available literature will be discussed.