Suicide by gabapentin overdose

Gabapentin is an antiepileptic drug that is prescribed for both FDA-approved and multiple off-label conditions, and has a relatively safe side-effect profile. Rare cases of overdose-related adverse effects have been reported in the literature. Described herein are the circumstances and autopsy findings of a 62-year-old woman with a history of depression, whose death was caused by intentional ingestion of excess gabapentin. The postmortem peripheral blood gabapentin concentration as determined by high-performance liquid chromatography/tandem mass spectroscopy was 88 μg/mL. Previously reported cases of individuals surviving gabapentin overdoses are discussed and compared with this case. Based on a review of the available literature, this appears to be the first published report of a death due solely to gabapentin toxicity.     

The extent of postmortem drug redistribution in a rat model.

The aim of this study was to investigate the postmortem redistribution of several drugs in a rat model and to examine if any of the pharmacological properties was related to the extent of this phenomenon. One of the following drugs: phenobarbital (phenobarbitone), acetaminophen (paracetamol), carbamazepine, codeine, verapamil, amphetamine, mianserin, trimeprazine (alimemazine) or chloroquine was administered together with nortriptyline orally to rats 90 min prior to sacrifice. Heart blood was sampled immediately before sacrifice and after 2 h postmortem, as it has previously been shown that this is sufficient time for postmortem concentration changes to occur in heart blood. Blood was also sampled from the clamped abdominal inferior vena cava (representing peripheral blood) and tissue samples were taken from lungs, myocardium, liver, kidney, thigh muscle, forebrain, and vitreous humor together with a specimen from the minced carcass. Drugs were analyzed by high performance liquid or gas chromatography. For phenobarbital, acetaminophen and carbamazepine the postmortem to antemortem blood drug concentration ratios were close to 1.0 and tissue concentrations were low. The postmortem to antemortem heart blood drug concentration ratio for chloroquine (6.9 +/- 1.5) was higher than for nortriptyline (3.5 +/- 0.3), and the remaining drugs (codeine, verapamil, amphetamine, mianserin, and trimeprazine) showed ratios of the same magnitude as nortriptyline. The postmortem to antemortem blood drug concentration ratios for both heart blood and blood from the vena cava and also the lung to antemortem blood drug concentration ratio were closely related to the apparent volume of distribution for the drugs studied (p < 0.001). Accordingly, an apparent volume of distribution of more than 3-4 L/kg is a good predictor that a drug is liable to undergo postmortem redistribution with significant increments in blood levels. The postmortem drug concentration in blood from vena cava was closely related to the antemortem blood level, confirming that among the postmortem samples, the peripheral blood sample was the most representative for the antemortem blood concentration.     

Unusual characteristic patterns of postmortem injuries

Animal scavenging is one of the most significant causes of postmortem injuries. A large variety of scavenging animals have been reported on in previous papers. Although postmortem injuries attributable to birds are well known in the case of "aerial burial," the custom in Tibet, few cases of bird scavenging have been reported. In the two cases discussed herein, postmortem injuries were attributed to crows. Both cases, shared characteristic patterns of postmortem injuries, and in both cases death was attributed to fire. Although massive tissue loss by the crow scavenging made it difficult to determine the cause of the death and rendered personal identification difficult, 1 mL of blood drawn from the intracranial cavity and DNA analysis enabled this information to be determined, albeit with some difficulty.     

The rise and rise of fentanyl in postmortem casework

Forensic toxicology laboratories are navigating a period of time with increasing drug overdose deaths, an opioid epidemic, the impact of the COVID-19 pandemic, and the illicit drug market flooded with novel psychoactive substances. In New York City, the Department of Forensic Toxicology has experienced a 56% increase in postmortem casework in the past decade with fentanyl detected in 80% of all overdose deaths. Over a period of 2.5 years, 15,638 postmortem cases were tested for the presence of fentanyl and fentanyl analogs using liquid-chromatography tandem mass spectrometry (LCMSMS). Fentanyl was detected in approximately one third of cases and of these 4447 cases with femoral blood. A twofold increase in cases with high concentrations of fentanyl (>100 ng/mL) was observed between 2021 and 2022. The minor metabolite and precursor chemical, 4-ANPP (4-anilino-N-phenethylpiperidine) may help differentiate between illicit and licit fentanyl. 4-ANPP blood concentrations were <10 ng/mL in 98% of the cases and the 4-ANPP:fentanyl ratio was <0.67 for 99.1% of blood specimens. Only six cases had 4-ANPP concentrations higher than the corresponding fentanyl blood concentration. This study also highlights, the changing fentanyl analogs found in postmortem cases since 2016 in NYC with the emergence of fluorofentanyl initially identified in 2020 and continuing to dominate in comparison with the prevalence of other analogs, many of which are no longer detected in casework. The detection of one of the latest drugs to be mixed with fentanyl, namely xylazine, has also increased in prevalence by 36.7% in 2022 compared with 2021.     

Pneumomediastinum and Soft Tissue Emphysema in Pediatric Hanging

Postmortem computed tomography (CT) is increasingly being used as a tool in forensic pathology. The exact value of postmortem imaging in detecting specific conditions has not yet been established, but in specific cases, it can be used as a diagnostic tool demonstrating findings that remain undetected during autopsy, as in this case. Pneumomediastinum and soft tissue emphysema were detected with postmortem CT in a 3‐year‐old girl after hanging. It was not found during autopsy. This radiological finding matches 3 adult cases previously described. It is assumed that in this case, the first reported in a child, hanging was the most likely cause as well. In the adult cases, it was interpreted as a vital sign; the person must have been alive to create a pressure gradient causing rupture of the alveoli. This case demonstrates one of the added values of postmortem imaging, the possibility of demonstrating findings that remain undetected during autopsy.     

The forensic science implications of site and temporal influences on postmortem blood-drug concentrations

The dependence of postmortem blood-drug concentrations on the collection site and on the postmortem interval before specimen collection has been studied. These studies consisted of both sequential sampling from the same collection site at defined time intervals and a comparison of the drug concentrations of postmortem blood simultaneously collected from various sites. A site and time dependence was observed for postmortem blood-drug concentrations. The heart blood-drug concentrations were, in general, significantly higher than those of peripheral specimens. As a result of this phenomenon, the analysis of peripheral blood specimens and solid tissues is often necessary before a definitive interpretation of postmortem toxicological analyses is possible.     

An Examination of the Postmortem Redistribution of Fentanyl and Interlaboratory Variability,

Fentanyl is a synthetic opioid agonist used for pain control. Often administered as a transdermal patch, it is an interesting drug for study of postmortem redistribution. We hypothesized that fentanyl concentrations would increase over time after death, as measured in blood drawn on the day prior to autopsy and in blood drawn at the time of autopsy in ten cases where fentanyl patches were identified at the scene. Concentrations were compared, and heart blood to femoral blood ratios were calculated as markers of postmortem redistribution. Fentanyl concentrations measured in peripheral blood drawn the day of autopsy (peripheral blood 2 [PB2]) were higher than those drawn the day prior to autopsy (peripheral blood 1 [PB1]) with a mean ratio (PB2/PB1) of 1.80. The ratio of heart blood concentrations (HB) to femoral blood concentrations drawn at autopsy (PB2) had a mean ratio (HB/PB2) of 1.08. Some cases had blood from the same source analyzed at two different laboratories, and concentrations of fentanyl in those samples showed inter‐ and intralaboratory differences up to 25 ng/mL. Postmortem fentanyl concentrations may be affected by antemortem factors, postmortem redistribution, and laboratory variability. Forensic pathologists must use caution in interpreting fentanyl levels as part of death investigation.     

Hypersensitivity myocarditis and hepatitis associated with imipramine and its metabolite, desipramine

We present two cases of myocarditis and hepatitis with histologic characteristics of hypersensitivity-mediated drug reactions associated with imipramine and its metabolite, desipramine. In one case, death was directly attributed to myocarditis; in the second case, the patient died of an acute myocardial infarct, but myocarditis may have played a contributory role. One patient was taking imipramine, and therapeutic concentrations of imipramine and desipramine were documented in postmortem blood. The other patient was receiving desipramine documented by in-patient hospital medication records. Both cases had liver lesions associated in the medical literature with adverse drug reaction to imipramine. Although myocarditis has been previously associated with amitriptyline, these cases appear to be the first reported in association with imipramine/desipramine. The fact that one patient was taking only desipramine suggests that it may be the offending agent.     

Fatal Oral Methylphenidate Intoxication with Postmortem Concentrations

Methylphenidate (MPD) is a widely prescribed stimulant used primarily for the treatment for attention‐deficit/hyperactivity disorder (ADHD). Suicide attempts involving MPD ingestion have been well described; however, deaths attributed solely to MPD ingestion have not been reported. A 62‐year‐old woman was found dead on her floor. The only discrepancy in among her medication quantities was that >three hundred 10 mg MPD tablets were missing. Analysis utilizing gas chromatography–mass spectrometry revealed elevated postmortem MPD peripheral and central blood, liver and vitreous humor concentrations. Considering both the central blood to peripheral blood ratio (0.89) and the liver to peripheral blood ratio (3.3), MPD does not appear subject to significant postmortem redistribution. With no other identifiable cause of death, we report what appears to be the first isolated MPD ingestion associated with a fatality.     

One hundred seventy two deaths involving the use of oxycodone in Palm Beach County

Oxycodone is a potent semi-synthetic narcotic prescribed for the management of pain. Previous investigators have reported that the abuse of oxycodone is most frequently seen in conjunction with the abuse of other drugs, although fatalities have been reported with oxycodone alone. We undertook a retrospective review of cases investigated by the Palm Beach County Medical Examiner's Office in which postmortem toxicologic studies indicated the presence of oxycodone. A total of 172 consecutive cases were studied, including 18 in which death was attributed to oxycodone toxicity, 117 to combined drug toxicity, 23 to trauma, 9 to natural causes and 5 to another drug or drugs. The postmortem blood concentrations of oxycodone overlapped among the groups. The mean blood oxycodone concentration among the cases of oxycodone toxicity was 0.69 mg/L, combined drug toxicity 0.72 mg/L and trauma 0.62 mg/L. Concentrations were lower in cases of deaths attributed to natural causes and to another drug or drugs (mean each 0.087 mg/L). Benzodiazepines, detected in 96 cases, were the most common co-intoxicants in the cases of combined drug toxicity, followed by cocaine, which was found in 41. The most frequently encountered benzodiazepine was alprazolam. This study confirms that deaths in which oxycodone is a factor are most commonly cases of combined drug toxicity. The high incidence of alprazolam as a co-intoxicant has not been previously recognized.     

Acute fatal acetaminophen overdose without liver necrosis

Two unusual cases of suicidal overdose of acetaminophen (paracetamol) without the usual extensive centrilobular necrosis of the liver are reported. Both cases were subjected to comprehensive drug screening by immunoassay, and a combination of gas chromatography with mass spectrometry, nitrogen detection, and electron capture detection. Acetaminophen was detected in both cases. No other drugs were detected in case #1, and only a small amount of olanzapine (<0.1 mg/L) was detected in case #2. No anatomical cause of death was identified in either case. If untreated, the normal outcome of a large acetaminophen overdose would be massive hepatic necrosis with delayed death and low blood and tissue acetaminophen concentrations. In contrast, particularly high postmortem acetaminophen concentrations were measured in both our cases with little hepatic tissue damage. For case #1, femoral blood acetaminophen 1280 mg/L, vitreous 878 mg/L, and liver 729 mg/kg; in case #2, cardiac blood 1220 mg/L, vitreous 779 mg/L, liver 3260 mg/kg, and gastric 11,500 mg/500 g. Acetaminophen was measured using high performance liquid chromatography with UV detection (254 nm) using 3-hydroxyacetanilide as the internal standard. The very high concentrations of acetaminophen is these cases but relatively little hepatic damage suggests an alternative, possibly cardiac, mechanism of death.     

Morbus Fahr--considerations on a case of sudden death

This paper presents 21 cases related to cyanide intoxication by oral ingestion. Cyanide concentrations in biological specimens are especially different from the type of postmortem specimens, and very important in interpreting the cause of death in postmortem forensic toxicology. Besides the detection of cyanide in autopsy specimens, the autopsy findings were unremarkable. Biological samples (0.2mL or equal to less than 10μg of cyanide) were analyzed colorimetrically for cyanide. In a series of 21 cyanide fatalities, the concentration ranges (mean±SD) of cyanide in heart blood, peripheral blood and gastric contents were 0.1-248.6mg/L (38.1±56.6mg/L), 0.3-212.4mg/L (17.1±45.1mg/L) and 2.0-6398.0mg/kg (859.0±1486.2mg/kg), respectively. The ranges of the heart/peripheral blood concentration ratio and gastric contents/peripheral blood concentration ratio were 0.3-10.6 (mean 3.4) and 3.4-402.4 (mean 86.0), respectively. From the difference of cyanide concentration and the concentration ratio of cyanide in different types of postmortem specimens, the possibility of the postmortem redistribution of cyanide and death by oral ingestion of cyanide could be confirmed. We reported cyanide fatal cases along with a review of literature.     

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.     

Distribution of morphine and morphine glucuronides in body tissue and fluids--postmortem findings in brief survival

An intoxication following administration of morphine, tramadol and atracurium in a suicide case is reported. The route of administration and the amount of the particular drug were known from the investigation of the death scene and the findings of the postmortem examination. Tramadol was present in the gastric contents as well as in blood, liver, kidney and brain samples, whereas the drug could not be detected in muscle. All body fluids and tissues investigated contained morphine as well as its 3- and 6-glucuronides with the exception of muscle tissue. The concentrations of morphine and its glucuronide metabolites were determined by LC/MS following solid phase extraction. Interestingly, the concentration of M6G in brain, liver and kidney were close to the concentration of M3G in the particular tissue. This phenomenon might be explained by a preferential hydrolysis of M3G or by a preferential formation of M6G postmortem. Measurement of morphine and M6G in femoral blood and cerebrospinal fluid may be a useful indicator in rapid deaths.     

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.     

Popliteal Vein Blood Sampling and the Postmortem Redistribution of Diazepam,Methadone, and Morphine

Postmortem redistribution (PMR) refers to the site‐ and time‐related blood drug concentration variations after death. We compared central blood (cardiac and subclavian) with peripheral blood (femoral and popliteal) concentrations of diazepam, methadone, and morphine. To our knowledge, popliteal blood has never been compared with other sites. Intracardiac blood (ICB), subclavian blood (SB), femoral blood (FB), and popliteal blood (PB) were sampled in 30 cases. To assess PMR, mean concentrations and ratios were compared. Influence of postmortem interval on mean ratios was also assessed. Results show that popliteal mean concentrations were lower than those for other sites for all three drugs, even lower than femoral blood; mean ratios suggested that the popliteal site was less subject to PMR, and estimated postmortem interval did not influence ratios except for diazepam and methadone FB/PB. In conclusion, our study is the first to explore the popliteal site and suggests that popliteal blood is less prone to postmortem redistribution.     

Fatal intoxication involving 2-methyl AP-237

Novel synthetic opioids contribute considerably to the opioid epidemic, especially with the frequent emergence of structurally similar compounds. This case report describes a fatal intoxication involving 2-methyl AP-237. A 54-year-old Caucasian male was found deceased from an apparent drug overdose. A plastic container labeled “2MAP” and a cut straw were found in the decedent's backpack at the scene. A white substance found in the container tested positive for fentanyl by field testing. According to his medical history, the decedent was treated for a drug overdose 3 years prior to his death. With no diagnostic findings at autopsy, the case was submitted for toxicological analysis. An unknown substance was detected in peripheral blood and urine using gas chromatography with nitrogen phosphorous detection (GC-NPD). Further testing was conducted using gas chromatography–mass spectrometry (GC–MS) and liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS) which confirmed the presence of 2-methyl AP-237 and potential metabolites in blood and urine. Quantitation by GC-NPD revealed concentrations of 2-methyl AP-237 in blood and urine at 480 ng/mL and 4200 ng/mL, respectively. The toxicological analysis also identified and quantitated alprazolam in the blood at 55 ng/mL. Additionally, the metabolism of 2-methyl AP-237 was investigated and three hydroxylated metabolites were identified in peripheral blood and urine. Limited literature is available for the detection and quantitation of 2-methyl AP-237 in postmortem specimens. Given the toxicological findings with unremarkable autopsy findings, this case is an example of a fatal intoxication involving 2-methyl AP-237.