Application to several suspected poisoning cases of a validated analytical method for the determination of muscarine in human biological matrices using liquid chromatography with high-resolution mass spectrometry detection.

Despite prevention efforts, many cases of mushroom poisoning are reported around the world every year. Among the different toxins implicated in these poisonings, muscarine may induce parasympathetic neurological damage. Muscarine poisonings are poorly reported in the current literature, implying a lack of available data on muscarine concentrations in human matrices. A validated liquid chromatography with high-resolution mass spectrometry detection (Orbitrap technology) method was developed to determine muscarine concentrations in human urine, plasma, and whole blood samples. Muscarine was determined using 100 µL of biological fluids, and precipitation was used for sample preparation. Liquid chromatography-mass spectrometry was performed using an Accucore Phenyl-X analytical column with the electrospray source in positive ion mode. Muscarine was quantitated in parallel reaction monitoring (PRM) mode with D9-muscarine as the internal standard. The method was validated successfully over the concentration range 0.1-100 µg/L for plasma and whole blood and 1-100 µg/L for urine, with acceptable precision and accuracy (<13.5%), including the lower limit of quantification. Ten real cases of suspected muscarine poisoning were successfully confirmed with this validated method. Muscarine concentrations in these cases ranged from 0.12 to 14 µg/L in whole blood,

Chlorophyllum molybdites poisoning on Reunion Island.

In France, mushroom picking is part of the culture. The practice is not without risk, as around 1300 people are poisoned each year by eating wild mushrooms on the French mainland. However, this practice is not part of local culture on Reunion Island, a French territory located in the Indian Ocean. Indeed, there are practically no reports of mushroom poisoning on Reunion Island. Here we describe, through a retrospective study, cases of mushroom poisoning recorded in the Indian Ocean toxicosurveillance system database from 2020 to 2021. Overall, 19 people were poisoned following wild mushroom ingestion on Reunion Island: 15 in 2020 and 4 in 2021. Six events were recorded: the majority of poisonings involved clusters (n = 5) during a shared meal (pan-fried), only one case was single mushroom poisoning by ingesting a raw mushroom. Of all patients, 15 cases presented a gastrointestinal irritant syndrome (latency between 30 min and 3 h). Chlorophyllum molybdites was positively identified by mycologists in 4 cases, suspected by emergency doctor in 1 case and in one self-declared case, Volvariella volvacea was consumed. Poisoning following ingestion of wild mushrooms does occur on Reunion Island, and Chlorophyllum molybdites is the main culprit.

Cyclopeptide mushroom poisoning: A retrospective series of 204 patients.

Cyclopeptide mushroom poisoning is responsible for 90%-95% of deaths from macrofungi ingestion. The main objectives of this study are to describe cases of cyclopeptide mushroom poisoning and to determine risk factors that may influence the severity/mortality of poisoned patients. We included all cases of amatoxin toxicity reported to two French Poison Centers from 2013 through 2019. We compared the severity with the Poison Severity Score (PSS) and the outcomes of patients using simple logistic regression and multinomial logistic regression. We included 204 cases of amatoxin toxicity. More than three-quarters developed an increase in AST and/or ALT (78.1%), and over half developed a decrease in prothrombin ratio (<70%: 53%) and/or Factor V (<70%: 54%). One-third developed an acute renal injury (AKI). Twelve patients (5.9%) developed post-poisoning sequelae (persistent kidney injury more than 1 month after ingestion and liver transplant). Five patients (2.5%) received a liver transplant, and nine died (4.4%). The mean time to onset of digestive disorders was shorter in PSS2 and PSS3-4 patients (10.9 ± 3.9/11.3 ± 6.3 h) than in PSS1 patients (14 ± 6.5 h; p < 0.05). Patients who died or developed post-poisoning sequelae had more frequent cardiovascular comorbidities compared with recovered patients (60.0% versus 29.5%; p < 0.01).

A Protocol for the Use of Case Reports/Studies and Case Series in Systematic Reviews for Clinical Toxicology.

Introduction: Systematic reviews are routinely used to synthesize current science and evaluate the evidential strength and quality of resulting recommendations. For specific events, such as rare acute poisonings or preliminary reports of new drugs, we posit that case reports/studies and case series (human subjects research with no control group) may provide important evidence for systematic reviews. Our aim, therefore, is to present a protocol that uses rigorous selection criteria, to distinguish high quality case reports/studies and case series for inclusion in systematic reviews. Methods: This protocol will adapt the existing Navigation Guide methodology for specific inclusion of case studies. The usual procedure for systematic reviews will be followed. Case reports/studies and case series will be specified in the search strategy and included in separate sections. Data from these sources will be extracted and where possible, quantitatively synthesized. Criteria for integrating cases reports/studies and case series into the overall body of evidence are that these studies will need to be well-documented, scientifically rigorous, and follow ethical practices. The instructions and standards for evaluating risk of bias will be based on the Navigation Guide. The risk of bias, quality of evidence and the strength of recommendations will be assessed by two independent review teams that are blinded to each other. Conclusion: This is a protocol specified for systematic reviews that use case reports/studies and case series to evaluate the quality of evidence and strength of recommendations in disciplines like clinical toxicology, where case reports/studies are the norm.

Identification of the origin of infantile saturnism based on lead isotopic and elemental ratios.

BACKGROUND: In France, the prevalence of childhood lead poisoning is becoming rare since the avoidance of lead in paints in 1949 and the gradual replacement of water pipes. Chronic lead toxicity is well known and is well correlated to blood lead concentration. AIM: Here we report a case of severe lead poisoning occurring in a young female child with a pica behavior. METHODS: A blood sample and four environmental samples were analyzed using inductively coupled plasma- mass spectrometry (ICP-MS). Lead concentration, lead isotopes and elemental ratios were compared. RESULTS: The determination of 208Pb/206Pb, 206Pb/207Pb and Cd/Pb has allowed us to identify the origin of lead poisoning. DISCUSSION-CONCLUSION: The source of contamination was eliminated and the child benefited from a psychological and medical follow up. Her outcome was positive. This case illustrated the potential interest of the use of elemental and isotopic ratios for clinical practice as the ICP-MS measurement has allowed a quick response and a rapid eviction of the contamination's source.

Second-generation antihistamines: a study of poisoning in children.

Background and objectives: The toxicity of second-generation antihistamines after an overdose by a child is still unknown. The objective of this study is to use data from Poisons Centres in France to describe the toxicity profile of second-generation antihistamines for children and to compare the severity of poisoning observed from these with a first-generation antihistamine.Method: This was a retrospective, multi-centre and observational study focusing on human cases of single-substance exposure to a second-generation antihistamine and to mequitazine, reported between 1 January 2001 and 31 December 2016 in Poisons Centres in France.Results: From a total of 9403 children included, 5980 were exposed to a second-generation antihistamine and 3423 were exposed to mequitazine. The severity of exposure to second-generation antihistamines in children is low: among the children followed until a known outcome, 9% of children were symptomatic and in 97% of cases, the symptoms shown were of a minor-level severity (primarily drowsiness or restlessness). Depending on the substance, children who ingested doses 16 to 69 times the maximum recommended therapeutic dose remained asymptomatic. No deaths or severe symptoms were observed. No cases of lengthening of the QT interval or arrhythmias were identified. Mequitazine led to more symptoms than other substances (14.8% symptomatic children vs. 7.5%, Odd ratio (OR): 2.3 (2.0-2.6), p < 0.0001), more symptoms of moderate intensity (1.4 vs. 0.2%, OR: 8.3 (4.1-18.5), p < 0.0001) and more hospitalisation (19.1 vs. 8.7%, OR: 2.5, 95% CI: (2.2-2.8), p < 0.0001).Conclusion: The severity of poisoning from second-generation antihistamines appears to be low among children and considerably lower than poisoning caused by mequitazine.

Severe poisoning with naproxen causing coagulopathy.

Non-steroidal anti-inflammatory drugs (NSAIDs) are well known for their most frequent side effects (digestive, renal and metabolic disorders) but are lesser known for other effects, such as coagulation disturbances. In this issue, we report the case of a 58-year-old woman who ingested 26 g of naproxen in a suicidal attempt and developed cardiovascular shock, hypocoagulability and thrombopenia. Her outcome was positive (extubation 3 days after admission [D3], correction of haemostatic disruptions on D5 and of thrombopenia on D6). Naproxen plasma concentration was at a toxic concentration of 1320 mg/L at 6 hours after drug ingestion. Only few cases of hypocoagulopathy are reported with the NSAIDs, and this is the first case that can be attributed to naproxen. A possible explanation of this phenomenon following naproxen ingestion is an inhibition of thromboxane A2, usually attributed to NSAIDs, combined with an inhibition of activation of downstream the cascade.

Ingestion of bar soap may produce serious injury: clinical effects and risk factors.

INTRODUCTION: Most household and body soaps have an alkaline pH (9-12). In addition to their foaming effect, they irritate the skin. This study aims to review soap exposure reported to the Angers Poison Control Centre. METHOD: A retrospective study of accidental or deliberate oral exposure to solid soaps reported to the Angers Poison Control Centre between 1 January 2000 and 1 April 2015. Poisoning severity was reassessed for each case according to the Poisoning Severity Score (PSS). RESULTS: 553 cases of exposure were recorded. In more than 40% of cases (n = 226), exposure occurred in community settings (retirement homes, nursing homes). Patients had a history of dementia in 220 cases (40%). The most common symptoms were labial oedema (28%, n = 153), oropharyngeal irritation (10%, n = 56), salivation (10%, n = 53), vomiting (9%, n = 48) and cough (8%, n = 45). Among symptomatic patients (n = 276), one patient died from aspiration pneumonia and one patient died from a cardiogenic shock following oropharyngeal oedema, vomiting, cough and bronchial obstruction. Patients with dementia were more often symptomatic (75% vs 34%, p < .001) and more frequently hospitalised (22% vs 0.8%, p < .001). They experienced more moderate to severe symptoms (8% vs 0%, p < .001). Mildly severe (PSS2, n = 14), highly severe (PSS3, n = 1) and fatal (PSS4, n = 2) poisoning were observed only in patients with dementia. CONCLUSION: Ingestion of soap bars is potentially serious, especially in patients with dementia. This type of soap should not be available to them in community settings and close monitoring should be considered in the event of oral exposure.

New evidence for oxetorone toxicity.

CONTEXT: Oxetorone is a serotonin antagonist antimigraine drug but literature relating to its toxic properties is poor. The aim of this study is to describe the toxicological profile of oxetorone and to highlight any relationship between clinical and analytical findings. MATERIALS AND METHODS: This is a retrospective and observational study of cases exposure to oxetorone, reported to the Angers Poison and Toxicovigilance Centre between January 2002 and May 2016. Severity was assessed using the Poisoning Severity Score (PSS). Cases where data were incomplete, where oxetorone was deemed not accountable, where clinical signs were linked mainly to a co-ingested drug or where the plasma concentration of oxetorone was negative were all excluded. RESULTS: We included 43 cases of exposure, 31 of whom were suicide attempts. The assumed ingested dose (60-3600 mg) was correlated to severity (rs = 0.45, p = 0.01). Symptoms of moderate severity (PSS2 = drowsiness, hypertonia, myosis, convulsions, arterial hypotension, QRS widening, QTc prolongation) were observed following ingestion of more than 600 mg of oxetorone (median dose =1200 mg) and severe symptoms (PSS 3 = coma, convulsions, QTc prolongation, QRS widening, ventricular tachycardia, arterial hypotension, cardiogenic shock) were observed starting from 1800 mg (median dose =2700 mg). In four cases, a secondary worsening of symptoms 10-48 h following ingestion was observed. Plasma oxetorone was measured in four patients. Severe symptoms were observed in the event of a concentration over 0.3 mg/L and the highest measured serum oxetorone level was delayed by 20-48 h following the ingestion for two cases. CONCLUSIONS: Several clinical and paraclinical parameters strongly point towards membrane-stabilising properties of the molecule and the risk of a delayed occurrence of symptoms or a secondary worsening.

Recreational phenethylamine poisonings reported to a French poison control center.

OBJECTIVES: Over the last decade, use of phenethylamines has become increasingly prevalent. This study aimed to describe typical aspects of phenethylamine poisoning in order to better inform patient care. METHODS: Phenethylamine poisoning cases reported to the Poison Control Center of Angers, France, from January, 2007 to December, 2013 were examined. Clinical findings were examined in 105 patients, including phenethylamine used, symptoms and final outcome. Patients were predominantly male (80%), with mean age 26±8 years. RESULTS: MDMA (38%), amphetamine (18%) and methamphetamine (14%) were the most commonly reported. Synthetic cathinones (10%) and the 2C series (7%) were also found. Substances most commonly associated with phenethylamine poisoning were cannabis (27%), ethanol (20%) and cocaine (9%). The most frequently reported symptoms included anxiety and hallucinations (49%), mydriasis and headache (41%), tachycardia (40%) and hypertension (15%). Complications such as seizures (7%), cardiac arrest (5%), toxic myocarditis (1%) and hemorrhagic stroke (1%) were also observed. Of the cases, the Poison Severity Score was: null or low, 66%, moderate, 21%, severe or fatal, 13%. Of the patients, 77% received hospital care and 12.4% were admitted to an intensive care unit. Analytical confirmations were obtained for all severe cases. While 93% of patients recovered, there were 5 deaths and 2 patients presented with neurological sequelae. CONCLUSIONS: Phenethylamine poisonings may be severe in young and healthy individuals. Physicians, toxicologists and analysts should be aware of new phenethylamine consumption trends in order to inform management of patient care and to contribute to a more responsive drug policy.