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.     

Toxicology and sudden infant death

One hundred thirty cases of sudden infant death occurring in Wayne County, Michigan, (population 2.7 million) were analyzed for possible drugs. The toxicological protocol has been outlined. Six cases were found to be positive, and in five of these the drugs found had been prescribed for a variety of illnesses. In one case methadone was found in the blood of an infant whose mother was undergoing methadone treatment for drug addiction, the drug being transmitted through breast milk. In none of the 102 cases of sudden infant death syndrome (SIDS) included in the study did the toxicological results affect the diagnosis. In our study, toxicological analyses never contradicted an initial diagnosis of SIDS, and, therefore, we feel that this diagnosis should be made promptly based on investigative and autopsy findings.     

Methadone toxicity causing death in ten subjects starting on a methadone maintenance program.

Methadone maintenance therapy is designed to reduce the need for addicts to use heroin or other illegal opiates. Death in patients starting on such a program has not previously been documented. We report the death of 10 persons who died within days of starting a methadone maintenance program administered by general practitioners. Their bodies were subject to a full autopsy by forensic pathologists, with a full toxicological examination. The mean starting dose had been 53 mg, which had been increased to a mean of 57 mg by the final dose. Death occurred after a mean of 3 days. The mean blood methadone concentration at death was 2.1 mumol/L. Complete toxicological analysis showed that six subjects had additional drugs present including two with alcohol, two with benzodiazepines and morphine, and one with benzodiazepines alone. Pathological examination revealed the presence of chronic persistent hepatitis in all subjects and bronchopneumonia in five. The causes of death were given as methadone toxicity or methadone toxicity in combination with bronchopneumonia. Our observations highlight the dangers of methadone in the first days of starting on a maintenance program, particularly when the starting doses are relatively high and subjects have no demonstrated tolerance to opiates.     

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.     

Fatal Intoxications Due to Administration of Isosorbide Tablets Contaminated with Pyrimethamine

In January 2012, 664 cases of pyrimethamine toxicity and 151 deaths were reported among cardiac patients that had recently received free medicines from pharmacy of Punjab Institute of Cardiology, Lahore, Pakistan. These patients, ages ranged from 58 to 75 years, were prescribed simvastatin, clopidogrel, aspirin soluble, isosorbide mononitrate, and amlodipine. On examination of medications being given to them, it was found that a particular batch of isosorbide mononitrate tablets was contaminated with 50 mg pyrimethamine. Cardiac patients were taking isosorbide contaminated with pyrimethamine twice daily (100 mg pyrimethamine/day), whereas therapeutic dose of pyrimethamine for malaria is 25 mg/week. Postmortem urine, cardiac blood, and femoral blood specimens of three deceased males were submitted to author's laboratory for analysis. Postmortem toxicological analysis revealed that pyrimethamine concentration fell within the range of 1–10 μg/mL by liquid chromatography. Clinical, autopsy, histopathological, and toxicological findings strongly suggested toxicity due to pyrimethamine accumulation that resulted in deaths of these cardiac patients.     

Suicidal yew ingestion

A 41-year-old man was found dead, lying in prone position on the ground near a parking area, where the car of the person was parked. Remarkable were the spasm-like hands of the decedent, cause of death was unknown. Primary an epileptical attack was assumed. A medicolegal autopsy was performed followed by histological and forensic toxicological analysis. Furthermore a plant anatomical investigation was applied. Autopsy revealed fragments of greenish needle-like leaves in the stomach and the intestines, but not in the colon. Plant anatomical investigation indicated the presence of yew. Histological findings were in concordance with the literature, in addition the investigation of bone marrow was performed for the first time. Forensic toxicological analysis revealed the presence of 3,5-dimethoxyphenol, the marker for intoxication with taxus baccata.This case reports the importance of medicolegal examinations in order to avoid misdiagnosis. Here the suspection of an epileptical attack as a possible cause of death was excluded by an autopsy, in addition an intoxication by yew leaves was proved.     

Toxicological findings in a multi-drug death involving propoxyphene, caffeine, phenacetin, acetaminophen and salicylate

The toxicological findings of a multi-drug related fatal poisoning are described here. A 35-year-old Caucasian male found dead on the kitchen floor was a known user of abused drugs and had been taking aspirin alone or in combination with phenacetin and caffeine for the relief of joint pains. The gross examination of the organs at autopsy revealed slight grooving of the uncus and various stages of necrosis in the renal papillae. Histological examination confirmed the gross appearance of pulmonary congestion and edema, cerebral edema and interstitial nephritis of the tubules. Toxicological evaluation of the blood and urine samples disclosed the presence of propoxyphene (51 and 250 mg/l), salicylate (185 and 2750 mg/l), caffeine (16 and 37 mg/l), and phenacetin (9.6 and 20 mg/l). Furthermore, acetaminophen also was present in the plasma (54 mg/l) and urine. A gas liquid chromatographic method for simultaneous analysis of phenacetin and caffeine utilizing a nitrogen phosphorus detector was proposed.     

The cocaine "body stuffer" syndrome: a fatal case

Body stuffer, sometimes called "mini packer", is the definition of someone who admits to or is strongly suspected of ingesting illegal drugs in order to escape detection by authorities, and not for recreational purposes or to transport the drug across borders. Cocaine is the drug most commonly involved in the body stuffer syndrome. Reported cases of body stuffer deaths are rare, however a fatality related to the ingestion of a plastic bag containing cocaine is described regarding a 17-year-old dealer. The authors describe how the cocaine body stuffer syndrome differs from the usual body packer. Histological and toxicological findings are examined and discussed for a better definition of this unique syndrome.     

Death of an infant involving benzocaine

This report describes the death of a four-month-old Hispanic male which may be related to benzocaine toxicity. A toxicological evaluation revealed benzocaine at a concentration of 3.48 mg/L, and postmortem methemoglobin of 36% (normal 0.4-1.5). Methemoglobinemia is a complication of benzocaine toxicity. In light of the toxicology findings, the coroner investigated the source of the benzocaine and discovered that the child was treated with Zenith Goldline Allergen Ear Drops containing 0.25% w/v benzocaine and 5.4% w/v antipyrine. There was an admission by a caregiver that on the day prior to the child's death, he had been treated with three times the prescribed dose. Blood benzocaine concentrations in nine other unrelated cases were determined and concentrations ranged from <0.05-5.3 mg/L (mean 1.48 mg/L). Seven of the nine cases were positive for drugs of abuse, and one additional case was described as a known drug user. Methemoglobin in these benzocaine positive cases ranged from 6-69%; however, methemoglobin concentrations in postmortem cases are frequently elevated and should be interpreted with caution. The unknown significance of the benzocaine, and the circumstances of the case raise questions about the ultimate attribution of this death to SIDS.     

Peri-mortem skin lesions caused by regurgitation of gastric juice. 2 case reports and differential diagnostic considerations

Two cases of regurgitation of gastric juice peri mortem are reported which resulted in lesions of the thoracic skin and led to the suspicion of being caused by another possibly dangerous chemical agent. In both cases, however, other causes of death could be established. Neither could any foreign chemical substances be detected by extensive toxicological investigations nor were any alterations of esophagus and gastric mucosa revealed in the course of the autopsy. Histological investigations demonstrated a circumscribed recent necrosis of the epidermis and dermis. Therefore, regurgitation of the acidic gastric content as the agent impairing the skin was most likely. The impressive histological appearance of the peri mortem regurgitation skin lesions lesions may be due to the circulatory arrest as well as stagnation of vital cellular reactions and repair mechanisms, dehydration of the altered tissue and postmortem permanence of the impairing agent.     

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.     

Perak, Malaysia, mass poisoning. Tale of the Nine Emperor Gods and rat tail noodles.

In October 1988, a series of food poisoning cases occurred in the State of Perak in Malaysia. Most of the victims were children. Ultimately 13 children between the ages of 2.5 and 11 years died. Epidemiological investigations showed that the probable source of the poison was Loh See Fun, a noodles in the shape of a rat's tail. All the deceased ate the noodles from one supplier. Clinical and pathological findings were similar in each case. Postmortem examination was performed in 11 cases. Toxicological examination on organs in 10 cases showed a high concentration of aflatoxin in tissues of the deceased. High levels of boric acid were excreted from most of the victims. Histological examination of the liver in these cases showed necrotic changes found in aflatoxin poisoning. Combination of the epidemiological, clinical, toxicological, and pathological findings pointed to the fact that there was a common toxin or toxins responsible for the deaths. These were thought to be a combination of boric acid and aflatoxin.     

Investigation of morphine and morphine glucuronide levels and cytochrome P450 isoenzyme 2D6 genotype in codeine-related deaths

Compared to morphine and morphine-6-glucuronide (M6G), codeine and its other major metabolites codeine-6-glucuronide and norcodeine have weak affinity to opioid μ-receptors. Analgesic effects of codeine are thus largely dependent on metabolic conversion to morphine by the polymorphic cytochrome P450 isoenzyme 2D6 (CYP2D6). How this relates to toxicity and post-mortem whole blood levels is not known. This paper presents a case series of codeine-related deaths where concentrations of morphine, M6G and morphine-3-glucuronide (M3G), as well as CYP2D6 genotype, are taken into account. Post-mortem toxicological specimens from a total of 1444 consecutive forensic autopsy cases in Central Norway were analyzed. Among these, 111 cases with detectable amounts of codeine in femoral blood were identified, of which 34 had femoral blood concentrations exceeding the TIAFT toxicity threshold of 0.3mg/L. Autopsy records of these 34 cases were retrieved and reviewed. In the 34 reviewed cases, there was a large variability in individual morphine to codeine concentration ratios (M/C ratios), and morphine levels could not be predicted from codeine concentrations, even when CYP2D6 genotype was known. 13 cases had codeine concentrations exceeding the TIAFT threshold for possibly lethal serum concentrations (1.6 mg/L). Among these, 8 individuals had morphine concentrations below the toxic threshold according to TIAFT (0.15 mg/L). In one case, morphine as well as M6G and M3G concentrations were below the limit of detection. A comprehensive investigation of codeine-related fatalities should, in addition to a detailed case history, include quantification of morphine and morphine metabolites. CYP2D6 genotyping may be of interest in cases with unexpectedly high or low M/C ratios.     

Methadone-related deaths in Norway

IntroductionThe use of methadone in opioid maintenance treatment (OMT) is potentially associated with a number of adverse effects and the risk of fatal toxicity. Increased methadone availability may lead to an increase in methadone-related deaths. We have investigated methadone-related deaths in Norway over the period 2000–2006.Materials and methodsMethadone-positive samples over the period 2000–2006 were identified from forensic toxicological investigations, and demographic and toxicological data were retrieved. The cases were cross-linked with the Norwegian Cause of Death Registry and regional OMT registers.ResultsA total of 312 individuals had died after taking methadone over the period 2000–2006, predominantly men with a mean age of 36. In 85% of cases (n = 264), the deceased had died of a methadone-related intoxication, most often in combination with other drugs, including benzodiazepines, cannabis and other opioids. Only 22% of the deceased had been in OMT at the time of death. A larger proportion of OMT patients had died of causes other than intoxications compared to those not in OMT (30% vs. 8%, respectively), most commonly related to disease.ConclusionsOne methadone-related death occurred, on average, every week over the time period investigated. Only 22% of the deceased were registered in opioid maintenance treatment (OMT) programs. The findings underline the need to control diversion of medication from OMT programs.     

n‐Ethyl Pentylone‐Related Deaths in Alabama

n‐Ethyl pentylone (NEP) is a chemical substance derived from cathinone. Synthetic cathinones are an evolving group of drugs with stimulating, mind‐altering effects sometimes referred to as novel or new psychoactive substances (NPS). There is scarce information in the medical literature regarding forensic cases in which NEP is detected in toxicological testing. We present four fatalities involving NEP from Alabama in 2017. Deaths were attributed to NEP toxicity in two cases (peripheral blood concentrations of 0.121 and 0.953 mg/L) and injuries caused by gunshot wounds in two cases (peripheral blood concentrations of 0.045 and 0.031 mg/L). One case involving NEP described an individual who exhibited classic CNS‐stimulant induced erratic behavior before being found dead. These cases enhance the forensic literature regarding specific NPS like NEP and provide contextual reference for professionals considering the significance of NEP in toxicological interpretation.     

The toxicological examination of the victims of the British Air Tours Boeing 737 accident at Manchester in 1985

The results of toxicological analyses of the body fluids of the victims from the accident involving the British Air Tours Boeing 737 in August 1985 are presented for carboxyhemoglobin, cyanide, and volatiles. All the victims except one had raised concentrations of carbon monoxide. All the victims had raised concentrations of cyanide. All the victims showed the presence of volatile substances in the blood. Autopsies revealed that all the victims had carbon particles in the trachea and bronchi. Thus, all the victims must have inhaled fire products in the burning aircraft cabin. Six victims had concentrations of carbon monoxide or cyanide in the blood that were neither fatal nor incapacitating; therefore, it is reasonable to suggest that these six victims survived for a comparatively short time and that there may have been other causes, in addition to toxic fumes, for their deaths. The other 48 victims must have survived long enough in the fire to accumulate incapacitating or fatal concentrations of carbon monoxide or cyanide or both. The effects of these substances found in the blood of each of the 48 victims must have combined to produce an insurmountable impediment to escape from the aircraft.     

Cutaneous current marks due to a stun gun injury

Histological changes of the skin following electrical injury with a stun gun have rarely been described. We report the case of a 61-year-old man who died after having been tortured with a stun gun during a robbery. At autopsy two reddish, dot-like lesions where found on the chest and histological examination revealed electric current-related changes. Only a few reports concerning micromorphological cutaneous changes following stun gun injury have been reported; therefore further investigations concerning the frequency and type of histological findings due to stun gun injuries will be necessary in order to provide sufficient characteristic data for a conclusive interpretation.     

Olanzapine concentrations in clinical serum and postmortem blood specimens--when does therapeutic become toxic?

The concentration of olanzapine (Zyprexa) was determined in 1653 clinical serum specimens during routine drug monitoring, and in 58 postmortem whole blood specimens as part of routine toxicological analysis. The analysis of olanzapine was performed by the solid-phase extraction of 1.0 mL of buffered serum or blood, followed by gas chromatography separation with nitrogen-phosphorus detection. The analysis of the clinical serum samples showed that 86% of positive serum values were within the range of 5 to 75 ng/mL, with a mean and median of 36 and 26 ng/mL, respectively. These data suggest that the concentrations of olanzapine expected during therapy may be higher than those previously reported. In 58 postmortem whole blood specimens the mean olanzapine concentration was 358 ng/mL with a range of 10 to 5200 ng/mL. Further, investigation of deaths involving olanzapine suggest that potential toxicity should be considered at concentrations above 100 ng/mL. Although the majority of the olanzapine-related deaths were associated with many other drugs, death primarily due to olanzapine toxicity was determined at concentrations in post-mortem blood as low as 160 ng/mL.