Clinical Toxicology最新文献

{"title":"Loperamide-induced severe cardiotoxicity: a toxicokinetic and toxicodynamic analysis derived from a case series and the published literature.","authors":"Úna Nic Ionmhain, Angela L Chiew, Michael Tierney, Judy Al Ahmad, Stefanie Pidcock, Faye Titania Whan, Lorraine Mackenzie, Michael S Roberts, Darren M Roberts","doi":"10.1080/15563650.2025.2459763","DOIUrl":"https://doi.org/10.1080/15563650.2025.2459763","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic loperamide overdose is associated with cardiotoxicity. We describe the toxicokinetics of loperamide and N-desmethyl loperamide, and their concentration-response relationship on cardiotoxicity in newly described and published cases.</p><p><strong>Materials and methods: </strong>We obtained serial loperamide and N-desmethyl loperamide concentrations, and corresponding electrocardiographic intervals in three episodes (two patients) of loperamide-related cardiotoxicity. A toxicokinetic and toxicodynamic analysis was undertaken that included data from previous publications to explore the relationship between these variables.</p><p><strong>Results: </strong>Patients presented with dizziness, bradycardia, loss of consciousness, and jerking or ventricular tachycardia after taking loperamide 320-400 mg/day for weeks or years. In one patient, ventricular tachycardia occurred on days two and three post-admission. Prolonged electrocardiographic intervals resolved after approximately five days. Admission loperamide concentrations were 5.37-288 μg/L and the terminal elimination half-lives were 21.3-38.7 h. Admission N-desmethyl loperamide concentrations were 87.67-256.34 μg/L and the terminal elimination half-life was 31.9-88.9 h. Overall, there were 42 loperamide and 35 N-desmethyl loperamide concentrations with paired electrocardiographic data, and the concentration-response relationship was derived using a maximum effect (Emax) model. Lower loperamide concentrations were associated with electrocardiographic abnormalities, compared to N-desmethyl loperamide concentrations. The total relative loperamide concentration, which combines both concentrations into a single value using <i>in vitro</i> inhibitory potencies at cardiac ion channels, out-performed either parent or metabolite concentrations alone for predicting cardiotoxicity on receiver operating characteristic curves.</p><p><strong>Discussion: </strong>Loperamide and N-desmethyl loperamide have long elimination half-lives causing prolonged cardiotoxicity. Higher loperamide and N-desmethyl loperamide concentrations are associated with prolonged electrocardiographic intervals.</p><p><strong>Conclusions: </strong>Patients with chronic loperamide overdose are at risk of cardiotoxicity that persists for days due to persistent loperamide and N-desmethyl loperamide concentrations. We believe patients with loperamide overdose need an admission electrocardiograph and continuous monitoring until electrocardiographic changes resolve.</p>","PeriodicalId":10430,"journal":{"name":"Clinical Toxicology","volume":" ","pages":"1-10"},"PeriodicalIF":3.0,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction.","authors":"","doi":"10.1080/15563650.2025.2486820","DOIUrl":"https://doi.org/10.1080/15563650.2025.2486820","url":null,"abstract":"","PeriodicalId":10430,"journal":{"name":"Clinical Toxicology","volume":" ","pages":"1"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paracetamol (acetaminophen) poisoning; consensus definitions of poisoning types and outcomes to be used in the clinical toxicology recommendations collaborative systematic review.","authors":"Angela L Chiew, David M Wood, Dazhe Cao, Adam Overberg, Katrin Faber, Anselm Wong, Ruben Thanacoody, Adam C Pomerleau, Sophie Gosselin, Ashish Bhalla, Davide Lonati, D Nicholas Bateman","doi":"10.1080/15563650.2025.2479721","DOIUrl":"https://doi.org/10.1080/15563650.2025.2479721","url":null,"abstract":"<p><strong>Introduction: </strong>Paracetamol (acetaminophen) poisoning is common, and many publications describe various outcomes and treatments. As internationally agreed definitions are non-existent to describe patterns of paracetamol overdose (acute, repeated supratherapeutic, chronic, or staggered), it is difficult to analyze outcomes between studies. The Clinical Toxicology Recommendations Collaborative was tasked to provide guidance on the management of paracetamol poisoning and formed the Paracetamol Workgroup. The Workgroup concluded that an agreed set of terms was needed to perform the systematic review and categorize the evidence.</p><p><strong>Methods: </strong>A modified Delphi process was employed to establish uniform definitions to categorize various patterns of paracetamol overdose.</p><p><strong>Results: </strong>Group consensus was reached for each one of the following standard definitions for each pattern of poisoning: acute, staggered, repeated supratherapeutic ingestions, and chronic for use in their upcoming systematic review. \"Acute\" ingestion represents an excessive amount of paracetamol ingested over a total time (from first paracetamol dose ingested to last paracetamol dose ingested) of less than 8 h. \"Staggered\" ingestion involves an excessive amount of paracetamol ingested over a total time period of between 8 h and 24 h. \"Repeated supratherapeutic ingestion\" describes ingestions exceeding the recommended daily dose for more than 24 h, and \"chronic\" ingestion includes both staggered or repeated supratherapeutic ingestions. \"High-risk overdoses\" are defined by either an ingested dose, that is greater than 500 mg/kg or 30 g (whichever is less), or an initial serum or plasma paracetamol concentration of greater than 300 mg/L (1,985 µmol/L) at 4 h on the Rumack-Matthew nomogram line.</p><p><strong>Discussion: </strong>The definitions established by the Paracetamol Workgroup will structure the upcoming systematic review, ensuring consistent categorization of studies within each ingestion pattern to enable clearer comparisons of treatments and outcomes.</p><p><strong>Conclusion: </strong>We encourage researchers to define overdose patterns and patients at increased risk of hepatotoxicity consistently and to include these definitions in publications to improve research reliability and comparability.</p>","PeriodicalId":10430,"journal":{"name":"Clinical Toxicology","volume":" ","pages":"1-5"},"PeriodicalIF":3.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on \"Comparison of children receiving extracorporeal treatments for poisoning at United States centers with and without a pediatric nephrologist\" by Cole et al.","authors":"Ju-Tae Sohn","doi":"10.1080/15563650.2025.2482122","DOIUrl":"https://doi.org/10.1080/15563650.2025.2482122","url":null,"abstract":"","PeriodicalId":10430,"journal":{"name":"Clinical Toxicology","volume":" ","pages":"1-3"},"PeriodicalIF":3.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Echocardiographic and clinical patterns in patients with acute carbon monoxide poisoning without cardiovascular and other chronic diseases.","authors":"Jarosław Szponar, Sylwia Goliszek, Anna Kujawa, Michał Tchórz, Anna Sutkowska, Anna Radoniewicz-Tchórz, Piotr Danielewicz, Agnieszka Witkowska, Anna Krajewska, Magdalena Majewska, Lidia Aftyka, Jarosław Bakiera","doi":"10.1080/15563650.2025.2456689","DOIUrl":"https://doi.org/10.1080/15563650.2025.2456689","url":null,"abstract":"<p><strong>Introduction: </strong>Severe carbon monoxide may impact the circulatory system, potentially leading to myocardial injury. This study aimed to assess left ventricular function via echocardiography in patients with acute carbon monoxide poisoning who were otherwise healthy.</p><p><strong>Methods: </strong>We conducted an observational, single-centre study involving consecutive patients hospitalized with carbon monoxide poisoning.</p><p><strong>Results: </strong>In a study of 112 consecutive patients with acute carbon monoxide poisoning, we identified a subset of 46 patients with moderate to severe poisoning. Among them, myocardial injury (defined by a peak high-sensitivity troponin T concentration >14.0 ng/L) was observed in 17 of 46 (36.9%) patients, forming the myocardial injury group. The remaining 29 patients formed the non-myocardial injury group. The echocardiographic assessment revealed no significant difference (<i>P</i> = 0.06) between the mean (±SD) left ventricular ejection fraction in the myocardial injury group (59.8 ± 5.4%), compared to the mean (±SD) in the non-myocardial injury group (62.9 ± 5.5%). However, the mean (±SD) left ventricular global longitudinal strain was significantly higher (<i>P</i> = 0.008) in the myocardial injury group (-20.1 ± 1.8%) compared to the non-myocardial injury group (-22.1 ± 2.4%). Patients in the myocardial injury group also exhibited significantly higher (<i>P</i> <0.001) mean heart rates (108.9 beats/min) compared to the non-myocardial injury group (87.6 beats/min). In addition, the mean plasma lactate concentration was significantly higher (<i>P</i> <0.001) in the myocardial injury group (1.95 mmol/L) compared to the non-myocardial injury group (1.2 mmol/L). There were no fatalities in either group.</p><p><strong>Discussion: </strong>Healthy patients with carbon monoxide poisoning who have myocardial injury may show minor changes in echocardiography in contrast to patients with co-morbidities.</p><p><strong>Conclusions: </strong>In patients with moderate to severe carbon monoxide poisoning, without concurrent chronic diseases, left ventricular global longitudinal strain was significantly lower in those with myocardial injury. However, these findings are based on a small cohort, necessitating further research.</p>","PeriodicalId":10430,"journal":{"name":"Clinical Toxicology","volume":" ","pages":"1-7"},"PeriodicalIF":3.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Authors' reply to comment on Cole et al. \"Comparison of children receiving extracorporeal treatments for poisoning at United States centers with and without a pediatric nephrologist\".","authors":"Jon B Cole, Anne M Kouri, Joshua D King, Travis D Olives, Nathaniel L Scott, Carrie L Oakland","doi":"10.1080/15563650.2025.2483385","DOIUrl":"https://doi.org/10.1080/15563650.2025.2483385","url":null,"abstract":"","PeriodicalId":10430,"journal":{"name":"Clinical Toxicology","volume":" ","pages":"1-2"},"PeriodicalIF":3.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive impairment associated with swelling of the isolated hippocampus related to dermal and inhalational exposure to chlorfenapyr.","authors":"Hongxin Zhang, Yang Liu, Na Meng, Shuhua Huo, Dongqi Yao, Hengbo Gao, Yingping Tian, Yu Gong","doi":"10.1080/15563650.2025.2458199","DOIUrl":"https://doi.org/10.1080/15563650.2025.2458199","url":null,"abstract":"","PeriodicalId":10430,"journal":{"name":"Clinical Toxicology","volume":" ","pages":"1-2"},"PeriodicalIF":3.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebrospinal fluid lactate gap in ethylene glycol poisoning.","authors":"Fumiya Inoue, Yuji Okazaki, Toshihisa Ichiba, Takuyo Chiba, Akira Namera","doi":"10.1080/15563650.2025.2482886","DOIUrl":"https://doi.org/10.1080/15563650.2025.2482886","url":null,"abstract":"","PeriodicalId":10430,"journal":{"name":"Clinical Toxicology","volume":" ","pages":"1-2"},"PeriodicalIF":3.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical effects of acute lamotrigine overdose (ATOM-10).","authors":"Angela L Chiew, Geoffrey K Isbister, Kiet Nguyen, Kristy McCulloch, Úna Nic Ionmhain, Katherine Z Isoardi","doi":"10.1080/15563650.2025.2471906","DOIUrl":"https://doi.org/10.1080/15563650.2025.2471906","url":null,"abstract":"<p><strong>Introduction: </strong>Lamotrigine overdose is not typically associated with severe toxicity. However, both severe toxicity and serotonin toxicity is occasionally reported following large ingestions. We aimed to investigate the clinical effects of lamotrigine overdose.</p><p><strong>Methods: </strong>This was a prospective observational study from July 2020-March 2024. Patients >14 years-old with acute lamotrigine overdose (≥2 g ingestion) were recruited from the Australian Toxicology Monitoring study or identified from three toxicology units. Data extracted included clinical features, lamotrigine concentrations, management, and outcomes.</p><p><strong>Results: </strong>Fifty-four patients were included, median age 29 years (IQR: 21-42 years), 37 (69%) were female. The median ingested dose was 4.8 g (IQR: 3.2-6.3 g) and 41 patients (76%) co-ingested other substances. The median maximum lamotrigine concentration was 18.5 mg/L (IQR: 12.4-25.0 mg/L) at a median time of 4.3 h (IQR: 3.2-10.8 h) post-ingestion. Clinical effects and their management included sedation in 44 (81%) with 29 patients (54%) endotracheally intubated, tachycardia in 39 (72%), hypotension in 21 (39%) with 15 (28%) receiving inotropes, and seizures in 11 (20%). Serotonin toxicity occurred in 23 (43%) patients with four having severe toxicity characterised by temperature >38.5 °C and/or rigidity treated with muscle paralysis. Higher peak lamotrigine concentrations were correlated with severe outcomes such as endotracheal intubation for coma (<i>P</i> <0.0001), patients with hypotension receiving inotropes (<i>P</i> = 0.0269) and patients developing seizures (<i>P</i> = 0.0002). Patients who co-ingested another serotonin agent (some in therapeutic doses) had a higher incidence of developing serotonin toxicity (22/33 [67%]) versus those who had not (1/21 [5%]); <i>P</i> <0.0001).</p><p><strong>Discussion: </strong>Severe toxicity was associated with higher peak lamotrigine concentrations. Serotonin toxicity was common in those who were exposed to another serotonergic agent.</p><p><strong>Conclusion: </strong>Coma, seizures and hypotension following lamotrigine overdose appeared to be concentration dependent. Serotonin toxicity occurred in those who co-ingested another serotonergic agent and was unrelated to lamotrigine concentration.</p>","PeriodicalId":10430,"journal":{"name":"Clinical Toxicology","volume":" ","pages":"1-7"},"PeriodicalIF":3.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling tenfold administration errors of oral risperidone solution in children.","authors":"Dania Takagi, Nir Friedman, Daniel Kurnik, Yael Lurie","doi":"10.1080/15563650.2025.2471916","DOIUrl":"https://doi.org/10.1080/15563650.2025.2471916","url":null,"abstract":"<p><strong>Introduction: </strong>In early 2023, the Israeli National Poison Information Center received reports of children exposed to tenfold dosing errors of oral risperidone solution. To assess the scope of this issue, we systematically searched for all similar cases reported to the Israeli National Poison Information Center. Our aims were to describe the occurrence and causes of such errors and explore potential preventive measures.</p><p><strong>Methods: </strong>Using the Israeli National Poison Information Center database, we retrospectively identified and reviewed cases of unintentional tenfold oral risperidone solution overdoses in children under 13 years of age between 1 January 2020, and 31 December 2023. We collected information about demographics, the circumstances of the administration error, and patient disposition and outcomes.</p><p><strong>Results: </strong>We identified 60 children (median age 7 years; IQR: 5.5-9 years; 73% boys) who were exposed to a tenfold error in the administration of oral risperidone solution. In 48% of cases, the error occurred upon the first administration. The main contributing factor to this dosing error appeared to be the discrepancy between the small dosing volume of the doses prescribed (approximately 0.25 mL) and the comparatively large syringe size provided by the manufacturer in the package (3 mL). We reported this issue to the Israeli Ministry of Health, which published a safety alert warning health care professional about such administration errors.</p><p><strong>Discussion: </strong>Oral medication solutions need to be measured individually and are therefore associated with a higher likelihood of dosing errors compared to tablets.</p><p><strong>Conclusion: </strong>Health care workers and caregivers need to be aware of the risk of dosing errors when administrating oral risperidone solution to children. Supplying appropriate dosing syringes with the medication bottle may mitigate the risks of such administration errors.</p>","PeriodicalId":10430,"journal":{"name":"Clinical Toxicology","volume":" ","pages":"1-5"},"PeriodicalIF":3.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}