Fatal hepatic failure following accidental tramadol overdose

A case of fatal overdose of tramadol is described, occurring in a 67-year-old man with painful rib fractures who accidentally ingested more than the recommended daily dose. The mode of death was acute liver failure due to fulminant hepatic necrosis. Post-mortem toxicology was negative apart from revealing a blood tramadol concentration well above the normal therapeutic range. This is the first report of fatal tramadol ingestion occurring in a therapeutic setting and also the first tramadol-related death where the mechanism was liver failure.     

Colchicine poisoning: case report of two suicides

Colchicine overdose is uncommon but potentially life threatening because of the high toxicity of the drug. Poisoning by colchicine may occur following ingestion of medication used in acute attacks of gout and inflammatory diseases. We describe two cases involving suicide by the ingestion of medications marketed in France. In case 1, only heart blood was taken after body external examination. In case 2 an autopsy was performed and heart blood, urine, gastric contents and bile were taken for toxicological analysis. Colchicine was assayed in biological specimens by an HPLC-DAD method, after extraction by dichloromethane at pH 8, adding prazepam as internal standard (IS). Analyses were performed on a Symetry C-8 column. Mobile phase was a gradient of acetonitrile/pH 3.8 phosphate buffer. Colchicine is eluted at 13.1 min and the method is linear for blood, urine and bile over the range 4-1000 ng/mL. LOQ is 4 ng/mL. The concentrations of colchicine detected are: case 1: heart blood 13 ng/mL; case 2: heart blood 66 ng/mL, urine 500 ng/mL, gastric content 12 ng/mL, bile 5632 ng/mL. Our findings are in the range of lethal concentrations previously described, but there is no correlation with the amount of ingested drug. Even after massive overdose, it could be impossible to detect colchicine in blood, and as there is a widespread enterohepatic recirculation before excretion in bile and feces, bile is the target sample to analyse. We conclude in both cases that the cause of death was suicide with colchicine. It appears very important to perform an autopsy in order to obtain bile, urine, heart blood and femoral blood.     

Acute overdose of zolpidem

Zolpidem (Ambien) is an imidazopyridine hypnotic recently introduced in the USA. We report a case of a fatal overdose of Ambien. A 68-year-old female ingested at least 30 tablets of 10 mg Ambien (300 mg). She was found dead at home. Toxicological analyses revealed blood concentration of 4.1, 19.3 and 2.3 μg/ml of zolpidem, meprobamate and carisoprodol, respectively.     

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.     

Fatal colchicine poisoning by accidental ingestion of meadow saffron-case report

A 62-year-old male died of colchicine poisoning after accidental ingestion of Colchicum autumnale (meadow saffron). He ate a salad of plant with green leaves regarded as wild garlic (Allium ursinum). A few hours later he developed symptoms of gastroenteritis and was admitted to hospital. In spite of gastric lavage, activated charcoal and supportive measures, multi-organ system failure developed over the next two days. Laboratory analysis showed highly elevated blood concentrations of hepatic enzymes, creatine kinase, lactate dehydrogenase and blood urea nitrogen, as well as leukocytopenia and thrombocytopenia. Mechanical ventilation, dopamine, noradrenaline, crystalloid solutions and fresh frozen plasma were applied but despite treatment the patient died five days after the ingestion. Post-mortem examination revealed hepatic centrilobular necrosis, nephrotoxic acute tubular necrosis, petechial bleeding in fatty tissue, blunt and shortened intestinal villi and cerebral toxic edema. Botanical identification of incriminated plant gave Colchicum autumnale which confirmed colchicine poisoning. Although the accidental ingestion of Colchicum autumnale is rare and to our knowledge only five such cases have been described in detail, this is the second fatal case in Croatia described in the last 3 years.     

Fatal colchicine poisoning

In two cases, after i.v. injections of colchicine serum concentrations of 170 ng/ml and 240 ng/ml were found before death. Colchicine was extracted from serum with the aid of Extrelut extraction columns and analysed using HPLC. Urine was also analysed and the findings were confirmed by drawing a UV-curve for colchicine using the stop-flow method. In one case, colchicine was still detectable in urine 10 days after injection.     

Fatal acetaminophen poisoning with evidence of subendocardial necrosis of the heart.

The authors describe a case of fatal acetaminophen overdose which occurred in a 16-year-old female. Her serum acetaminophen concentration 11.5 h postingestion was 154 mg/L. Antidotal therapy was unsuccessful, and after 9 days she died. Autopsy findings included centrilobular zonal liver necrosis, acute proximal renal tubular necrosis, and diffuse alveolar pulmonary damage. Her heart was transplanted into a young woman with congenital heart disease. The recipient expired 14 days after the transplant as a result of sepsis complicating bowel ischemia. The transplanted heart showed extensive subendocardial myocyte necrosis related to acetaminophen toxicity and not rejection.     

Epithelial cell mitotic arrest--a useful postmortem histologic marker in cases of possible colchicine toxicity

Following ingestion of 30 mg of presumed benztropine (Cogentin) a 39-year-old male developed nausea, vomiting and diarrhea. His admission to hospital was soon followed by collapse and death. Histological examination, however, revealed increased numbers of mitotic figures in otherwise normal epithelial cells of the esophagus and bronchioles, a feature characteristic of colchicine toxicity. Subsequent toxicological analyses confirmed the presence of colchicine in the urine, but not in the blood. A dispensing error had resulted in substitution of colchicine for Cogentin. Histological findings had, therefore, provided evidence of colchicine toxicity and had guided subsequent toxicological evaluation. In suspected cases of colchicine toxicity, histological samples should, therefore, be taken from multiple sites along the gastrointestinal and respiratory tract in addition to other organs and tissues so that diagnostic morphological changes can be looked for.     

A fatal overdose of the ergot derivative cabergoline

A 79-year-old woman, with Parkinson's disease treated with cabergoline, was admitted to a hospital due to jaundice and weakness. She was found confused, absent minded, and died after 2 weeks. Autopsy showed an extrahepatic bile duct adenocarcinoma with spread to the gall bladder, the liver, and regional lymphnodes. While cleaning the hospital bed after her death, the nurses found several tablets hidden in the bed. Biological samples obtained at the autopsy were screened for common drugs and narcotics. Several drugs such as buprenorphine, codeine, paracetamol, and propranolol were detected in the blood at therapeutic levels. A method to determine cabergoline in whole blood and other forensic matrices was developed, and further investigations determined cabergoline concentrations in whole blood and liver tissue of 94 and 3100 microg/kg, respectively. The blood concentration was 100 times above the therapeutic level reported on cabergoline in plasma and in combination with her symptoms, suggest she took a fatal overdose of cabergoline.     

秋水仙碱在急性中毒豚鼠体液和组织中的检测及分布

目的建立生物检材中秋水仙碱的液相色谱/串联质谱检测方法,研究秋水仙碱急性中毒在豚鼠体内的分布,为秋水仙碱中毒的法医学鉴定提供方法和评价依据。方法以4mg/kg剂量秋水仙碱给豚鼠灌胃染毒,2～8h死亡,用LC-MS/MS测定体液和组织中秋水仙碱的含量。结果秋水仙碱在豚鼠各体液和组织中含量从高到低依次为胆汁、尿液、胃、脾、肺、肾、心、胰、肝、肾上腺、睾丸,心血中秋水仙碱的含量最低。结论所建方法准确、灵敏,适用于体内痕量秋水仙碱的检测。胆汁和尿液是体内检测秋水仙碱的较佳检材。     

Fatal cyclobenzaprine overdose with postmortem values

There are only two published cases of overdose with postmortem blood cyclobenzaprine concentrations, both with confounding factors. We report two additional cases of fatal cyclobenzaprine overdose with postmortem values. Case 1: a 56-year-old female was found in full cardiopulmonary arrest after a verbal suicide threat to a friend. Postmortem blood concentrations were cyclobenzaprine 0.96 mg/L and diazepam 0.3 mg/L. Case 2: a 37-year-old male was found in full arrest by a family member after an intentional ingestion of cyclobenzaprine. Postmortem blood concentrations were cyclobenzaprine 0.8 mg/L and ethanol 0.174 gm/dL. The concentrations of diazepam and ethanol reported in these two patients were not found in quantities usually associated with a fatal outcome, suggesting that the cyclobenzaprine was the primary cause of the fatality. Additionally, the blood was drawn from a femoral site, so that postmortem redistribution is not a likely factor. Blood concentration of > or = 0.8 mg/L cyclobenzaprine may be associated with a fatal outcome.     

Colchicine poisoning by accidental ingestion of meadow saffron (Colchicum autumnale): pathological and medicolegal aspects

Although intoxications with colchicine, the alkaloid of Colchicum autumnale (meadow saffron), are well known, in most cases the intoxications are evoked by oral or parenteral preparations traditionally used as medication against gout. The accidental ingestion of Colchicum autumnale, on the other hand, is a rare event and has to our knowledge only twice been described in detail. We report a further case in which two persons confused this highly poisonous plant with wild garlic (Allium ursinum), a popular spice in the Central European cuisine. While one person merely complained about a 3-day episode of nausea, vomiting and watery diarrhea, the second person died of multi-organ system derangements 48 h after the ingestion of the colchicum leaves. At autopsy hemorrhagic lung oedema, hypocellular bonemarrow, centrilobular fatty necrosis of the liver and necrosis of the proximal convoluted tubuli of the kidneys were observed. A colchicine concentration of 7.5 micrograms/ml was found in the bile whereas no substance was detected in the postmortem blood.     

Report of a fatal, acute tripelennamine intoxication.

A death resulting from tripelennamine overdose in a 19-year-old male Caucasian is reported. The patient died 7 h after ingesting approximately twenty 50-mg tripelennamine tablets. A concentration of 1.0 mg/100 ml was found in the blood. All tissue concentrations were measured by ultraviolet spectroscopy and verified by gas-liquid chromatography. Significant findings included pulmonary edema and multiple small petechial hemorrhages in the soft tissue of the scalp.     

Case report of a fatal intoxication by citalopram

Citalopram is an antidepressant drug within the group of the selective serotonin reuptake inhibitors (SSRI). It is widely prescribed both in Europe and in United States, and it has always been considered a "safe" drug as pure intoxication with lethal outcome is rare, and most cases of overdose, even with high doses of citalopram ingested, are reported to have an uneventful course.We report the case of a young woman found dead at home. She had been prescribed citalopram by her family doctor 3 weeks before her death for a depressive syndrome. Police found in her house 3 empty blister packages of 28 citalopram tablets (20 mg) and 2 bottles of citalopram oral solution (4%, 15 mL each). The autopsy findings were unremarkable. Nasal swabs, blood from femoral vein, urine, bile and tissue samples were collected for toxicologic investigation. Citalopram separation was performed by solid/liquid method, using Bond-Elute columns. The extracts were analyzed by GLC and GC/MS methods. The toxicologic analysis showed high levels of citalopram in all the examined fluids and tissue samples (blood concentration: 11.60 mg/L). No other drugs and alcohol were detected. Our data confirm that if no other drug is involved, fatal complications occur only after ingestion of very high doses. However, there is no predefined "toxic dose," and the conditions under which the overdose occurs can be very important. We report the exact concentrations of the citalopram in the organs, and wethink that this can be useful in the cases where the blood samples were not available (ie, carbonized or decomposed body).     

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.     

Bupropion Overdose Resulted in a Pharmacobezoar in a Fatal Bupropion (Wellbutrin®) Sustained‐release Overdose: Postmortem Distribution of Bupropion and its Major Metabolites

Bupropion (BUP) overdose commonly causes generalized seizures and central nervous system depression. The case of a 28‐year‐old woman who died from a massive lethal overdose with sustained‐release bupropion (Wellbutrin^® 300 mg) is herein presented. The autopsy revealed the presence of a pharmacobezoar consisting of at least 40 tablets in the stomach. Determination of bupropion and its active metabolites (hydroxybupropion, threobupropion, erythrobupropion) was achieved by a liquid chromatographic mass spectrometry (LC‐MS/MS) method. Postmortem concentrations for bupropion, hydroxybupropion, threobupropion, and erythrobupropion were obtained in intracranial blood, urine, bile, liver, kidney, and vitreous humor. In this case, intracranial blood level of the parent drug was 1.9 mg/L. Threobupropion was the most abundant metabolite in both blood and urine, 59.3 and 890.6 mg/L. Tissue distribution showed the highest concentration in the liver, 12.3 mg/kg. The 0.8 bupropion concentration ratio vitreous/blood suggested that vitreous could be a valuable specimen for toxicological analysis should postmortem blood be unavailable.     

Interpretation of postmortem digoxin levels: evaluating a "corrective factor" for postmortem blood digoxin concentration

Interpretation of postmortem serum digoxin levels is made difficult above all by a possible prefinal or postmortem rise in digoxin concentrations in the blood. To compensate for this postmortem increase, Eriksson et al. (1984) divided the level of postmortem digoxin in femoral venous blood by a factor of 1.5; in the opinion of these authors, postmortem digoxin levels still exceeding "therapeutic levels" after division by 1.5 are an index of digoxin overdose. The diagnostic value of this "correction factor" was investigated. In 56 cases with documented digoxin medication, samples of postmortem femoral venous blood were taken and the level of digoxin determined. In none of the cases had there been a clinical diagnosis of digoxin intoxication. Fifty percent of the measured values were above "therapeutic levels" (0.7 ng/ml to 2.2 ng/ml). Following division by 1.5, 20% of the cases still showed levels exceeding 2.2 ng/ml; the highest "corrected" value was 4.44 ng/ml. Taking into account the length of time between final dosage and death, individual differences in sensitivity to digitalis glycoside, and the complexity of ante- and postmortem dispersion processes, we concluded for the cases we studied that an (undetected) digoxin overdose was not even likely in those cases whose postmortem values after division by 1.5 lie above "therapeutic levels". The "correction factor" proposed by Eriksson et al. (1984) is only of limited diagnostic value; at best the "corrected" values can give an approximate indication of the corresponding antemortem serum digoxin concentrations. In particular, "corrected" values only a little above "therapeutic levels" could not confirm suspicion of an overdose with sufficient certainty.     

Polydrug fatality involving metaxalone

A 29-year old female with a history of depression was found dead in a hotel room. The death scene investigation found empty pill bottles and an empty liter bottle of wine. Metaxalone, a centrally acting muscle relaxant, along with citalopram, ethanol, and chlorpheniramine were identified in the postmortem samples and quantitated by gas chromatography-mass spectrometry. The concentration of metaxalone in femoral vein blood was 39 mg/L. The heart blood concentration was 54 mg/L. Femoral vein blood concentrations of citalopram and chlorpheniramine were 0.77 mg/L and 0.04 mg/L, respectively. Ethanol levels were 0.13 g/dL in vitreous and 0.08 g/dL in heart blood. Other tissue samples were also analyzed. The authors consider the metaxalone concentrations toxic and potentially fatal. The citalopram concentrations were lower than those reported in fatal cases for this drug alone. Death was ascribed to polydrug abuse/overdose with metaxalone a major contributor. This represents the first reported case to our knowledge in which a metaxalone overdose significantly contributed to death.     

Toxicological aspects of fatal chloroquine poisoning over a period of several days

The anti-inflammatory and antimalarial drug chloroquine is said to be one of the most frequently used drugs to commit suicide in the Orient and Far East. After the ingestion of large amounts of this 4-amino-chinoline derivate, signs of cardiac conduction disturbances are evidence of cardiotoxic action. For clinical treatment, hemoperfusion by activated charcoal has rather than hemodialysis proved to be partly effective for the removal of the toxic substance. Following a suicidal overdose of chloroquine tablets in a 13-year-old boy, we could confirm the efficiency of hemoperfusion by continued toxicologic examinations. The total elimination was nevertheless slow. Due to high postmortem concentrations in the blood and tissues, we believe that chloroquine is deposited and especially concentrated in the reticulohistiocytary system of the liver. Death after 5 days of clinical treatment in this case may be referred to as the first cardiac arrest with irreversible hypoxic damage of the brain.     

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.