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.     

Colchicine poisoning resulting from accidental ingestion of meadow saffron (Colchicum autumnale)

A rare case of colchicine poisoning resulting from accidental ingestion of meadow saffron (Colchicun Autumnale) is reported. The plant can frequently be found in the woods of the Northern Hemisphere (1), also in Japan. A 48-year-old male was admitted to hospital complaining of vomiting, nausea and diarrhea following ingestion of the plant and died in four days. The most striking histological findings were metaphasic mitotic figures in the mucosa of the large intestine and the liver. Colchicine was detected in the bile with high-performance liquid chromatography/sonicspray ionization mass spectrometry (HPLC/SSI-MS).     

Colchicine Extract Suicidal Lethal Poisoning Confirmation Using High‐Resolution Accurate Mass Spectrometry: A Case Study

A case of suspected acute and lethal intoxication caused by colchicine has been reported. The woman was hospitalized after her suspicion of suicidal poisoning by a rare autumn crocus (Colchicum autumnale). Suspected colchicine poisoning was confirmed using a novel UHPLC method with a modern reversed‐phase stationary phase with a sub 2‐micron superficial porous particle size combined with a QTOF mass spectrometer. Sample preparation procedure included the addition of propiverine as internal standard, protein precipitation using methanol and solid phase extraction. High‐resolution MS only and targeted MS/MS modes are reported for the qualitative analysis and screening of other potential drugs of abuse in blood samples. All Ion MS mode was used for quantitative determination of colchicine afterward. The concentration of colchicine in the blood sample was approximately 41 ng/mL, and more than 200 μg/mL of the plant extract used for the suicide.     

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.     

Paraquat (gramoxone) poisoning in south-west Hungary, 1977-1984. Toxicological and histopathological aspects of group intoxication cases

Fifty-six cases of paraquat poisoning were examined during the 8 years 1977-1984. The ratio of cases of accidental to intentional ingestion of the poison was 1:1; 23.2% of the total (13/56) survived several months or years. In 1983, 11 subjects accidentally drank 10-30 ml of gramoxone; eight of 11 died in 2 weeks. Toxicological investigations demonstrated rapid elimination of poison from the blood, as well as prolonged fixation of paraquat in the lung, kidney, liver, and spleen tissues. Histological examinations showed multiorgan failure from renal tubular necrosis and pulmonary hemorrhage with alveolar epithelial injury. Pulmonary proliferative changes were present in only two cases who survived 7 and 10 days and in which artificial ventilation was utilized.     

Unexpected double lethal oleander poisoning

Nerium oleander is a very popular urban ornamental plant in Europe, but it is also extremely dangerous because it contains several types of glycosides, accidental ingestion of which can cause cardiac arrhythmias and even deaths. The rarity of such cases makes it difficult to think of oleander poisoning without evidences that suggest this possibility as the cause of the unexpected death. This report concerns the discovery of the bodies of 2 young people, a man and a woman, in a forest in conditions of extreme malnutrition. Medicolegal investigations showed neither pathologic nor traumatic causes of death, but the presence of vegetal remains in the stomach was noticed. A common toxicological analysis resulted negative, but the implementation of more detailed investigations showed the presence of digoxin in the blood of both cadavers, excluding the possibility of a pharmaceutical provenience of digoxin, this laboratory result was interpreted as evidence of ingestion of oleander, which contains oleandrine, the cross reaction of which with digoxin is widely described in the literature. Identification of the 2 subjects, which occurred after 4 years, strengthened the hypothesis of accidental poisoning by oleander because it was ascertained that the 2 young people were vegans--extreme vegetarians who reject the ingestion of foods of animal origin and live by eating only what they find in nature.     

A case of fatal poisoning with the aconite plant: quantitative analysis in biological fluid.

In recent years recorded cases of plant poisoning have become rare, this may in part be due to the possibility of plant ingestion not being indicated at the beginning of an investigation. Aconitum napellus (aconite, Wolfsbane, Monkshood) is one of the most poisonous plants in the UK. It contains various potent alkaloids such as aconitine, isoaconitine, lycaconitine and napelline. Ingestion of Aconitum plant extracts can result in severe, potentially fatal toxic effects. This paper describes the analytical findings in a recent death in the UK. resulting from deliberate ingestion of Aconitum napellus extract. The concentrations of aconitine measured by HPLC-DAD in the post mortem femoral blood and urine were 10.8 micrograms/L and 264 micrograms/L, respectively. The aconitine concentration in the ante mortem urine was 334 micrograms/L and was estimated to be 6 micrograms/L in the ante mortem serum. Hence, accidental, suicidal or homicidal poisoning due to the ingestion of plant material remains a possibility and should be borne in mind when investigating sudden or unexplained death.     

Accidental potassium dichromate poisoning. Toxicokinetics of chromium by ICP-MS-CRC in biological fluids and in hair

Intoxications by chromium (Cr) compounds are very life threatening and often lethal. After oral ingestion of 2 or 3g of hexavalent Cr (Cr(VI)), gastrointestinal injury, but also hepatic and renal failure, often occurs which each leads to a fatal outcome in most patients. Cellular toxicity is associated with mitochondrial and lysosomal injury by biologically Cr(VI) reactive intermediates and reactive oxygen species. After Cr(VI) has been absorbed, there is not much that can be done except to control the main complications as the treatment is only symptomatic. The biotransformation of Cr(VI) to Cr(III) reduces the toxicity because the trivalent form does not cross cellular membranes as rapidly. In fact, more than 80% of Cr(VI) is cleared in urine as Cr(III). We report the case of a 58-year-old male patient who was admitted to hospital after accidental oral ingestion of a 30 g/L potassium dichromate (the estimated amount of ingested Cr is about 3g). ICP-MS equipped with a collision/reaction cell (CRC) and validated methods were used to monitor plasma (P), red blood cells (RBCs), urine (U) and hair chromium. For urine the results were expressed per gram of creatinine. After 7 days in the intensive care unit, the patient was discharged without renal or liver failure. P, RBC and U were monitored during 49 days. During this period Cr decreased respectively from 2088 μg/L to 5 μg/L, 631 μg/L to 129 μg/L and 3512 μg/g to 10 μg/g. The half-life was much shorter in P than in RBC as the poison was more quickly cleared from the P than from the RBC, suggesting a cellular trapping of the metal. Hair was collected 2 months after the intoxication. We report a very rare case of survival after accidental Cr poisoning which has an extremely poor prognosis and usually leads to rapid death. For the first time, this toxicokinetic study highlights a sequestration of chromium in the RBC and probably in all the cells.     

A case of fatal aconitine poisoning by Monkshood ingestion

Accidental aconitine poisoning is extremely rare in North America. This report describes the confirmation of a case of accidental aconitine poisoning using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The case involved a 25-year-old man who died suddenly following a recreational outing with friends where he consumed a number of wild berries and plants including one that was later identified as Monkshood (Aconitum napellus). Postmortem blood and urine samples were available for analysis. All routine urine and blood toxicology screens were negative. The LC-MS/MS method allowed sensitive quantification of aconitine, the main toxin in A. napellus, and showed 3.6 and 149 microg/L in blood and urine, respectively. These concentrations were similar to that reported in other aconitine-related deaths. This case illustrates the dangers of consuming unidentified plants, and documents concentrations of aconitine in blood and urine in a fatal case of A. napallus-related poisoning.     

Determination of ethylene glycol tissue content after fatal oral poisoning and pathologic findings

A 23-year-old comatose man who had drunk an unknown amount of ethylene glycol was admitted to the hospital 5 hours after ingestion. The initial plasma ethylene glycol concentration was 116.2 mg/100 ml. A severe metabolic acidosis was present. Despite aggressive therapy with ethanol, hemodialysis, and intensive care support, the patient died 27 hours after poisoning. The plasma ethylene glycol concentration immediately before death was 35.9 mg/100 ml. Brain edema and acute renal tubular necrosis were evident at postmortem examination. Oxalate crystals were identified in both organs. Ethylene glycol content or concentration was determined in tissues and biologic fluids.     

Homicidal Paraquat Poisoning

Paraquat poisoning usually results from suicide, occupational, or accidental exposure. Herein, we report a rare fatal case of homicidal paraquat poisoning. A 58‐year‐old man was poisoned by taking paraquat‐mixed medicine and wearing paraquat‐soaked underwear. In the absence of a history of paraquat exposure, the patient was misdiagnosed with pulmonary infection and scrotal dermatitis and died of respiratory failure 24 days after the initial exposure to paraquat. Ultra‐performance liquid chromatography‐tandem mass spectrometry (UPLC‐MS/MS) was applied to detect and quantify paraquat in postmortem specimens. The concentration of paraquat in postmortem specimens from high to low is lung (0.49 μg/g), brain (0.32 μg/g), kidney (0.24 μg/g), liver (0.20 μg/g), cardiac blood (0.11 μg/mL), and stomach wall (<LOQ). Identification of homicidal paraquat poisoning is not easy for a clinician or a forensic pathologist, it is important to consider the possibility of paraquat poisoning when patients suffer from rapidly aggravating pneumonia of unknown origin.     

顶空气质联用法测定腐败血、肝检材中CO

目的研究CO中毒腐败血、肝组织检材中CO的HS/GC/MS检测。方法用HS/GC/MS法分析碳氧血红蛋白(COHb)血的线性范围。配制10%、30%、50%、70%浓度COHb血样,分别在室温、冷藏、冷冻条件下保存,分别在当日、第4、14、45d进行测定,比较实验结果。腐败肝组织由雄性健康家兔通CO气体致死,当天解剖,家兔肝常温隔绝空气保存并放35d至腐败,期间进行不定期顶空测定分析。结果制备的COHb血在0-100%之间有良好的线性关系Y=2.4X+2.2(r=0.9995)。以此方法测定家兔CO中毒致死的COHb新鲜血的浓度和4℃下放置45dCOHb腐败血,结果表明温度对血样中COHb%的测定影响最大。采用HS/GC/MS法检测,每次只需0.25ml血样或1g肝脏,分析一次时间只需3min,均可检测出新鲜检材和常温放置45d的腐败肝组织检材CO的含量。结论HS/GC/MS法能检出CO中毒的腐败生物检材中CO。     

Carbofuran poisoning of pregnant woman and fetus per ingestion

A case of carbamate pesticide poisoning of a pregnant woman by carbofuran ingestion is presented. The mother recovered from the poisoning in the hospital but necrosis of the fetus was found. Toxicological findings of the liver, brain, and kidney of the fetus revealed carbofuran in concentrations comparable with the mother's blood. Our findings in the case contribute to the research on permeation of the placental barrier by chemical substances.     

Determination of formic acid tissue and fluid concentrations in three fatalities due to methanol poisoning

Three fatalities caused by methanol ingestion are reported. Admission blood methanol concentrations ranged from 0.28 to 4.6 g/L. Two patients had been admitted after a significant delay (>20 hours), and one patient was observed within 90 minutes following ingestion. Formic acid levels were determined in blood samples at admission and ranged from 302 to 680 mg/L. The patients died 44, 55, and 82 hours after poisoning. Formic acid determinations in postmortem tissues were performed by a gas chromatograph method. The authors found great variability in formic acid distribution among the patients and among organs.     

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.     

Detection of S-methylfenitrothion, aminofenitrothion, aminofenitroxon and acetylaminofenitroxon in the urine of a fenitrothion intoxication case

A 23-year-old male attempted suicide by ingesting approximately 50 ml of 5% fenitrothion emulsion, and vomited soon afterwards. He was admitted to a hospital about 3 h after ingestion. He recovered and was discharged from hospital 3 days after admission. The serum cholinesterase activity (normal range: 175-440 I.U.) was only 29 at 3 h, 32 at 1 day, 59 at 2 days and 75 at 3 days after ingestion. Fenitrothion and its metabolites in the body fluids were extracted by an Extrelut column extraction method, detected by a gas chromatograph equipped with either a hydrogen flame ionization detector or a flame photometric detector, and confirmed by a gas chromatograph-mass spectrometer. Fenitrothion concentration in the blood was 169.5 ng/g at 3 h after ingestion. The half life of blood fenitrothion concentration was found to be about 4.5 h. Fenitrothion metabolites, 3-methyl-4-nitrophenol, aminofenitrothion, aminofenitroxon, acetylaminofenitroxon and S-methylfenitrothion, were detected in the urine samples. All of them except S-methylfenitrothion were detected in the urine samples collected up to 62 h after ingestion. It would appear therefore that fenitrothion poisoning can be determined by detection and analysis of the metabolites in urine even if fenitrothion has not been detected in the blood.     

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.     

Accidental methylene chloride fatality

A case of accidental methylene chloride poisoning by inhalation is presented. The methylene chloride concentration in post-mortem blood was 29.8 mg% as determined by a headspace gas-chromatography technique. The accidental death was attributed to improper ventilation of vapors.