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.     

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.     

Colchicine poisoning: case report of two homicides

Deaths resulting from the oral ingestion of colchicine are occasionally associated with suicides and therapeutic toxicity. However, homicidal deaths in which this drug is used are extremely rare. Two homicides in which colchicine was used are reported.     

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).     

Death following acute poisoning by moclobemide

A fatality due to ingestion of a reversible inhibitor of monoamine-oxidase A (MAO-A) is reported. Moclobemide is generally considered as a safe drug far less toxic than tricyclic anti-depressants. However, severe intoxications may result from interactions with other drugs and food such as selective serotonin reuptake inhibitors (SSRIs), anti-Parkinsonians of the MAOI-type (e.g. selegiline) or tyramine from ripe cheese or other sources. In the present case, high levels of moclobemide were measured in peripheral blood exceeding toxic values reported so far in the scientific literature. The body fluid concentrations of moclobemide were of 498 mg/l in peripheral whole blood, 96.3 mg/l in urine while an amount of approximately 33 g could be recovered from gastric contents. The other xenobiotics were considered of little toxicological relevance. The victim (male, 48-year-old) had a past history of depression and committed one suicide attempt 2 years before death. Autopsy revealed no evidence of significant natural disease or injury. It was concluded that the manner of death was suicide and that the unique cause of death was massive ingestion of moclobemide.     

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.     

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.     

Fatal intoxications in the Nordic countries. A forensic toxicological study with special reference to young drug addicts

Fatal intoxications in the 15-34 age group in the five Nordic countries during the years 1984 and 1985 (Sweden only in 1984) were investigated. The known drug addicts were studied separately. The highest incidence of intoxications, calculated per 10(5) population, was found in Finland (11.3), followed by Denmark (10.3), Sweden (8.5), Iceland (7.2) and Norway (6.6). The percentage of intoxications caused by drugs was 92 in Denmark, 71 in Norway, 66 in Sweden, 50 in Finland and 17 in Iceland. Ethanol intoxications were seen 5-7 and 2-3 times as frequently in Finland and in Iceland, respectively, than in the other three countries. Carbon monoxide intoxications accounted for two-thirds of all fatal intoxications in Iceland. Drug addicts accounted for 62% of all fatal intoxications in the Danish material. The corresponding figures were 33% in the Norwegian, 16% in the Swedish and 5% in the Finnish material. No deaths in drug addicts were found in Iceland. Most drug addicts in Denmark, Norway and Sweden died of hard drugs and most in Norway and Sweden, from heroin or morphine, whereas in Denmark other strong analgesics, such as methadone, dextropropoxyphene and ketobemidone, accounted for 40% of all hard-drug-related fatal intoxications. To a certain extent the results reflect differences in the legal autopsy routines in the various Nordic countries. However, the ascertainment of drug addicts is assumed to be near-complete in each country.     

Fatal poisonings with propoxur

The insecticide propoxur (2-isopropoxyphenyl-N-methylcarbamate) acts by blocking cholinesterase. This inhibition is fast and, unlike that brought about by organophosphorus compounds, reversible. The toxicity of propoxur to man is stated to be low compared with that of parathion. Only a small number of fatal intoxications have been published; at the Würzburg University Institute of Legal Medicine eight cases have been observed since 1978. In seven cases death occurred after deliberate oral ingestion of solutions of propoxur with suicidal intent, while in the other, intoxication was accidental, following inhalation of an aerosol containing propoxur. Organs and body fluids were investigated toxicologically and histologically. The results are presented and discussed. Special attention is paid to the combination of propoxur and alcohol.     

Fatal intoxications in a Swedish forensic autopsy material during 1992-2002

Compilations of substances detected in fatal intoxications are important in order to observe changes in intoxication patterns, to monitor effects of preventive work and to discover new trends in drug usage. The aim of the present study was to describe the current pattern of substances detected in fatal intoxications in Sweden. Fatal intoxications investigated at the Department of Forensic Chemistry, Link?ping, Sweden, during 1992-2002, were analysed. All suicides, uncertain cases and accidents where the cause of death were fatal intoxications (ICD-9: E950, E980 and E859) were included and substances detected in more than 50 fatal intoxications (in femoral blood) were listed. For each substance, a cut off value was set, above which concentrations were considered toxic. Fatal intoxications were detected by forensic-chemical analyses in 12% (6998/60,314) of the forensic autopsies during the study period. Among the suicides, an average of 3.8 substances were detected per case, the corresponding figure for uncertain cases and accidents were 3.5 and 4.1 substances, respectively. Ethanol was by far the most frequently detected substance, detected in 43% (3039) of the fatal intoxications, of which 32% (960) had toxic concentrations, followed by propoxyphene, detected in 27% (1863) of the fatal intoxications of which 74% (1370) had toxic concentrations. The number of cases where ethanol and propoxyphene were detected decreased during the study period. Moreover, other CNS-active drugs such as antidepressants, analgesics and anxiolytics were also frequently detected. The drugs with high proportions of cases with toxic concentrations detected were propoxyphene, amitriptyline, zolpidem, carisoprodol, alprazolam, thioridazine, methadone and ketobemidone. Selective serotonin reuptake inhibitors (SSRI) and tricyclic antidepressants (TCA) were detected in 12% (833) and 10% (665), respectively. A significantly (P <0.001) higher proportion of cases where TCA were detected had toxic concentrations when compared with cases where SSRI were detected (64% versus 31%).     

Pesticide intoxications in the Centre of Portugal: three years analysis

Pesticides are used in most countries around the world to protect agricultural and horticultural crops against damage. Poisoning by these toxicant agents occurs as a result of misuse or accidental exposure, and also by oral ingestion (voluntary or not). In Portugal, pesticide intoxications are still a cause of death, found in a considerable number of cases. The authors retrospectively examined the cases of pesticide poisoning in the Centre of Portugal, from autopsies performed in the Forensic Pathology Service of Coimbra's Delegation of the National Institute of Legal Medicine (NILM) and from other autopsies carried out in the Centre of Portugal, as well as some samples taken in hospitals in cases of suspected intoxication. In this study, the positive cases have been especially studied, in order to identify the pesticide used, as well as the etiology. The frequency of intoxications and its distribution by sex and age were also analyzed. Between January 2000 and December 2002, the Forensic Toxicology Laboratory received 639 pesticide analysis requests. In 2000, in a total of 149 analysis requests, 30 cases were positive, 63.3% from male individuals and 36.7% from female. In 2001, the analysis requests increased to 240 as well as the positive cases (43), 74.4% from male individuals and 25.6% from female and in 2002, the total cases analyzed also increased to 250, with 38 positive (73.6% from male individuals and 26.4% from female). Among the pesticides, organophosphorus insecticides still constitute the most important class detected in forensic intoxications, representing 63% of the total positive cases, followed by herbicides, with 33% of the positive results. Quinalphos is the most important organophosphorus insecticide, present in 32 of the 111 positive cases, followed by the herbicide paraquat, detected in 31 cases. The study emphasizes the increasing number of pesticide analyses, particularly relevant for the organophosphorus compounds and herbicides. Intoxication suspicion, accidental or voluntary, seems to be the most common cause of the incidents, for which analyses are requested, but it is also evident that the putative cause is unknown in a large number of cases. Therefore, more stringent legislation and enforcement regarding the sale and distribution of these toxic substances are needed.     

Sudden death due to a paraganglioma of the organs of Zuckerkandl

A 20-year-old woman died suddenly in a hospital emergency room after presenting with nausea, vomiting, back pain, and hypertension. At autopsy, an extra-adrenal pheochromocytoma (paraganglioma) of the organs of Zuckerkandl was found, with microscopic focal myocardial necrosis similar to that described in death from adrenal pheochromocytomas. Tumors of the organs of Zuckerkandl are extremely rare; less than 100 such cases have been reported in the world's literature, and only six, including the present case, have presented as a sudden, unexpected death. The symptoms of catecholamine storm may mimic those of acute drug intoxications, leading to misdiagnosis by both clinical physicians and pathologists.     

Aortic dissection after ingestion of "ecstasy" (MDMA)

The authors report a case of aortic dissection and cardiac tamponade in a 29-year-old man after ingestion of ecstasy (methylenedioxymethamphetamine, MDMA) at a "rave" party. There was no history of hypertension, myxoid heart disease, or other risk factors for aortic dissection in the deceased, although a minor degree of cystic medial necrosis was noted on histologic examination of the aorta. Autopsy toxicology revealed low residual levels of MDMA in the blood about 48 hours after ingestion of the drug. This case report describes a probable association between MDMA ingestion and aortic dissection in a previously well young adult. The likely mechanisms are discussed, and the difficulties in diagnosing this complication are highlighted.     

Variable adverse effects in subjects after ingestion of equal doses of Argyreia nervosa seeds

As the new drug Spice hit the market in 2006 and was a hot topic in the media, the general issue of legal highs has been brought to the attention of a large number of (young) people. One of these so called legal highs are the seeds of Argyreia nervosa, also known as Hawaiian Baby Woodrose, which contains the psychotropic alkaloid lysergic acid amide (LSA). A study was designed to assess how driving ability is affected by Argyreia nervosa. However, the study could not be continued due to severe adverse effects in 3 of 4 subjects, such as cardiovascular dysregulation in two and a psychosis like state in one subject. All of the participants recovered completely within 9h after ingestion. Despite body normalized doses interindividually highly differing reactions in type and intensity were observed. Furthermore, fluctuating alkaloid contents in seeds and multi-drug intoxications make the use of this legal high far more dangerous than commonly believed.     

Fatal intoxication with 1,4-butanediol: Case report and comprehensive review of the literature

A fatal case of 1,4-butanediol (1,4-BD) oral ingestion is reported here, in which a 51-year-old man was found dead in his bed. According to the police report, the deceased was a known drug user. A glass bottle labeled (and later confirmed to be) “Butandiol 1,4” (1,4-BD) was found in the kitchen. Furthermore, the deceased's friend stated that he consumed 1,4-BD on a regular basis. The autopsy and histological examination of postmortem parenchymatous organ specimens did not revealed a clear cause of death. Chemical-toxicological investigations revealed gammahydroxybutyrat (GHB) in body fluids and tissues in the following quantities: femoral blood 390 mg/L, heart blood 420 mg/L, cerebrospinal fluid 420 mg/L, vitreous humor 640 mg/L, urine 1600 mg/L, and head hair 26.7 ng/mg. In addition, 1,4-BD was qualitatively detected in the head hair, urine, stomach contents, and the bottle. No other substances, including alcohol, were detected at pharmacologically relevant concentrations. 1,4-BD is known as precursor substance that is converted in vivo into GHB. In the synoptic assessment of toxicological findings, the police investigations and having excluded other causes of death, a lethal GHB-intoxication following ingestion of 1,4-BD, can be assumed in this case. Fatal intoxications with 1,4-BD have seldom been reported due to a very rapid conversion to GHB and, among other things, non-specific symptoms after ingestion. This case report aims to give an overview to the published of fatal 1,4-BD-intoxications and to discuss the problems associated with detection of 1,4-BD in (postmortem) specimens.     

Histomorphometric indices of the pancreas in intoxication with alcohol and narcotics

The results of histomorphometric examinations of the pancreas in drug- and alcohol-addiction as well as in acute intoxications are described. They show that, in chronic alcoholic intoxication as compared with opiomania, there are more pronounced interlobular sclerosis and lipomatosis, which is manifested by an enlarged middle lobe of the stroma (containing fat and connective tissue fibers), by a higher density of islands of Langerhans and by their higher sectional area. Autolysis and edema of the stroma are more severe in an acute intoxication with drugs than in other cases of fatal outcome. A possibility is demonstrated to differentiate between various types of the so-called long-term exogenous intoxication and to discriminate between different types of thanatogenesis typical of various cases of acute intoxications. Data are presented that demonstrate the advantage of the quantitative analysis of histological preparations over the qualitative one.     

Methyl alcohol poisoning in Trabzon (Turkey)

The aim of this retrospective study was to examine methyl alcohol intoxications in Trabzon (Turkey) and to determine any relations between the laboratory results and histopathologic changes. A total of 4492 forensic autopsies were performed from 1998 to 2008. Thirteen of the cases (0.3%) were because of methanol poisoning, and all were men. Their ages ranged from 25 to 62 years. The blood methanol concentrations ranged widely, from 15 to 482 mg/dL. In six cases, poisoning was because of consumption of the alcoholic beverage "Raki," while in five cases, poisoning was because of the ingestion of cologne. The products consumed were unknown in the other two cases because of insufficient history and data records. Mortality because of methanol poisoning may be prevented/decreased with the implementation of some precautions, such as public education regarding the harms of methyl alcohol, routine monitoring of the vendors that sell alcoholic beverages and cologne, and appropriate legal retribution for the illegal production of methanol.     

Increased lung weight in fatal intoxications is not unique to opioid drugs

Fatal intoxications with opioids are known to be associated with an increased lung weight, as well as with brain and pulmonary edema and urinary retention. However, there is evidence to suggest that fatal intoxications with non-opioid substances are also associated with increased lung weight; however, the latter aspect has not been comprehensively analyzed. To determine to what extent opioid and non-opioid substances are associated with increased lung and brain weight, we studied these organs in cases where the cause of death was attributed to intoxication with a single agent. Using data from cases autopsied at the National Board of Forensic Medicine (NBFM) in Sweden from 2009 through 2019 where the cause of death was attributed to a single substance, we created models of combined lung weight and brain weight. The models used age and sex as predictors as well as nested varying effects for the specific intoxicant and category of intoxicant. Suicidal hanging with negative toxicology cases served as controls. The population majority was male among both intoxications (68%) and controls (83%). The most common single substance group was opioids. All tested substances were associated with heavier lungs than controls, with the largest effect in the opioid group. Our findings show that several substances are associated with increased lung weight and that among intoxication deaths there is no difference in expected brain weight between substances. Hence, heavy lungs, without a reasonable explanation, should prompt a broad toxicological screening.     

Fatalities in the bathtub

A retrospective analysis concerning deaths in the bathtub was carried out in the Institute of Legal Medicine in Hamburg. The study includes 245 death cases between 1971 and 1988 (1% of all autopsies). 66 cases proved to be natural deaths, 76 were classified as suicides, 39 as accidents and 13 as homicides; 51 fatalities remained unclear with respect to one of these groups. Among the natural deaths sudden cardiac deaths were dominating (n = 39), among the suicides the intoxications (n = 37) and electrocutions (n = 20), and among the accidents the intoxications by carbon monoxide (n = 17) and electrocutions (n = 12). Out of 13 homicides only 2 were committed directly in the bathtub: One by drowning of a child and one by electric current via a hair dryer; in the other cases the dead body was put into the bathtub post mortem. About 50% of the victims were alcoholized. Signs of drowning were present in about 40% of all cases; the most frequent finding was emphysema aquosum.