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Hypernatremia is an increase in serum sodium concentration above 145 mmol/L. There are many causes of elevated sodium levels in the blood serum. One is incorrect actions performed by medical staff. The symptoms of excessively high serum sodium levels depend on the severity of hypernatremia, the rate of its increase and the accompanying volume disorders. Severe symptoms include altered consciousness, increased muscle tone and reflexes, convulsions, psychomotor hyperactivity or drowsiness (up to coma), respiratory failure, and even death. We present the case of a 45‐year‐old man who took seven tablets of a blood pressure‐lowering drug, and paramedics subsequently administered a concentrated solution of table salt to induce vomiting. However, vomiting did not occur, leading to hypernatremia. Ultimately, the man survived but developed persistent cognitive dysfunction, including disordered short‐term memory and encoding and retrieval of information from long‐term memory, weakening of attention function and fatigue, and disorders in abstract thinking. The patient's family went to the prosecutor's office to investigate the possibility of medical malpractice. Experts found that the paramedics' actions were incorrect. Although it has been known for many years that table salt solutions should not be used to induce vomiting, unfortunately, both laypeople and medical professionals are still using this technique. Iatrogenic salt poisoning may end not only in serious health complications but also in legal consequences. [ABSTRACT FROM AUTHOR]

Metabolomics aims for comprehensive characterization and measurement of small molecule metabolites (<1700 Da) in complex biological matrices. This study sought to assess the current understanding and usage of metabolomics in laboratory medicine globally and evaluate the perception of its promise and future implementation. A survey was conducted by the IFCC metabolomics working group that queried 400 professionals from 79 countries. Participants provided insights into their experience levels, knowledge, and usage of metabolomics approaches, along with detailing the applications and methodologies employed. Findings revealed a varying level of experience among respondents, with varying degrees of familiarity and utilization of metabolomics techniques. Targeted approaches dominated the field, particularly liquid chromatography coupled to a triple quadrupole mass spectrometer, with untargeted methods also receiving significant usage. Applications spanned clinical research, epidemiological studies, clinical diagnostics, patient monitoring, and prognostics across various medical domains, including metabolic diseases, endocrinology, oncology, cardiometabolic risk, neurodegeneration and clinical toxicology. Despite optimism for the future of clinical metabolomics, challenges such as technical complexity, standardization issues, and financial constraints remain significant hurdles. The study underscores the promising yet intricate landscape of metabolomics in clinical practice, emphasizing the need for continued efforts to overcome barriers and realize its full potential in patient care and precision medicine. [ABSTRACT FROM AUTHOR]

Introduction: Common major co-formulants in glyphosate-based herbicides, polyethoxylated tallow amine surfactants, are suspected of being more toxic than glyphosate, contributing to the toxicity in humans. However, limited information exists on using polyethoxylated tallow amine concentrations to predict clinical outcomes. We investigated if plasma concentrations of glyphosate, its metabolite and polyethoxylated tallow amines can predict acute kidney injury and case fatality in glyphosate poisoning. Methods: We enrolled 151 patients with acute glyphosate poisoning between 2010 and 2013. Plasma concentrations of glyphosate, its metabolite, aminomethylphosphonic acid, and polyethoxylated tallow amines were determined in 2020 using liquid chromatography-tandem mass spectrometry. Associations between exposure and poisoning severity were assessed. Results: Plasma concentrations of glyphosate and aminomethylphosphonic acid demonstrated good and moderate performances in predicting acute kidney injury (≥2), with an area under the receiver operating characteristic curve of 0.83 (95% CI 0.69–0.97) and 0.76 (95% CI 0.59–0.94), respectively. Polyethoxylated tallow amines were detected in one-fifth of symptomatic patients, including one of four fatalities and those with unsaturated tallow moieties being good indicators of acute kidney injury (area under the receiver operating characteristic curve ≥0.7). As the number of repeating ethoxylate units in tallow moieties decreased, the odds of acute kidney injury increased. Glyphosate and aminomethylphosphonic acid concentrations were excellent predictors of case fatality (area under the receiver operating characteristic curve >0.9). Discussion: The 2.7% case fatality rate with 49% acute, albeit mild, acute kidney injury following glyphosate poisoning is consistent with previously published data. A population approach using model-based metrics might better explore the relationship of exposure to severity of poisoning. Conclusions: Plasma concentrations of glyphosate and its metabolite predicted the severity of clinical toxicity in glyphosate poisoning. The co-formulated polyethoxylated tallow amine surfactants were even more strongly predictive of acute kidney injury but were only detected in a minority of patients. [ABSTRACT FROM AUTHOR]

Introduction and purpose: Digoxin, a cardiac glycoside derived from Digitalis lanata, has stood as a cornerstone in the treatment of various cardiovascular disorders for centuries. This study aims to delve into the demographic aspects, clinical characteristics, and outcomes associated with Digoxin poisoning. By drawing upon a dataset involving 22 patients hospitalized for Digoxin intoxication at the Clinical Department of Toxicology and Cardiology in Lublin, Poland, spanning from April 2014 to December 2023, our investigation seeks to provide an understanding of this issue. Brief description of the state of knowledge: Despite the efficacy of Digoxin, the potential risk of intoxication, especially in the elderly, necessitate a comprehensive examination. Age-related changes, such as declining renal function, electrolyte imbalances, comorbidities and polypharmacy affect how drugs like Digoxin work. The symptoms of Digoxin poisoning can manifest in various organ systems such as cardiovascular, gastrointestinal, nervous system, highlighting the importance of prompt recognition to seek medical attention. Methods and results: In our study, we analyzed data from 22 patients hospitalized due to Digoxin intoxication, focusing on demographic aspects, clinical characteristics and outcomes. The cases of Digoxin poisoning were categorized according to several factors, including the quantity and nature of substances consumed, the cause of intoxication, gender, age brackets, health conditions, peak serum Digoxin levels, length and outcomes of hospitalization. Conclusions: Our study provides insights into the characteristics and outcomes of patients hospitalized due to Digoxin intoxication. The findings underscore the association of Digoxin poisoning, and emphasize the importance of monitoring serum levels to prevent adverse outcomes. As Digoxin continues to be relevant in treating cardiovascular conditions, our study calls for careful management and monitoring. [ABSTRACT FROM AUTHOR]

BACKGROUND: Liquid chromatography-high-resolution mass spectrometry (LC-HR-MS) has emerged as a powerful analytical technology for compound screening in clinical toxicology. To evaluate the potential of LC-HR-MS3 in detecting toxic natural products, a spectral library of 85 natural products (79 alkaloids) that contains both MS2 and MS3 mass spectra was constructed and used to identify the natural products. Samples were analyzed using an LC-HR-MS3 method and the generated data were matched to the spectral library to identify the natural products. METHODS: To test the performance of the LC-HR-MS3 method in different sample matrices, the 85 natural product standards were divided into three groups to separate structural isomers and avoid ion suppression effects caused by co-elution of multiple analytes. The grouped analytes were spiked into drug-free serum and drug-free urine to produce contrived clinical samples. RESULTS: The compound identification results of the 85 natural products in urine and serum samples were obtained. The match scores using both MS2 and MS3 mass spectra and those using only MS2 mass spectra were compared at 10 different analyte concentrations. The two types of data analysis provided identical identification results for the majority of the analytes (96% in serum, 92% in urine), whereas, for the remaining analytes, the MS2-MS3 tree data analysis had better performance in identifying them at lower concentrations. CONCLUSION: This study shows that in comparison to LC-HR-MS (MS2), LC-HR-MS3 can increase the performance in identification of a small group of the toxic natural products tested in serum and urine specimens.

Rationale: Tramadol (T) is a strong painkiller drug that belongs to the opioid analgesic group. Several accidental intoxication cases after oral administration of T have been reported in the past decade. Tramadol, its derivatives, and metabolites present information‐limited mass spectra with one prominent peak representing the amine‐containing residue; therefore, their structural determination based on both electron impact mass spectrometry (EI‐MS) and ESI‐MS/MS spectra could be misleading. Methods: A novel analytical method for the structural elucidation of tramadol, its four homologs, and its two main phase I metabolites (N‐desmethyltramadol and O‐desmethyltramadol) was developed using chemical modification and liquid chromatography–high‐resolution tandem mass spectrometry (LC‐HR‐MS/MS) with Orbitrap technology. Results: After chemical derivatization, each of the investigated T series exhibited informative mass spectra that enabled better exposition of their structures. The developed method was successfully implemented to explicitly identify the structures of tramadol and its N‐desmethyltramadol metabolite in urine samples at low ng/mL levels. Conclusions: An efficient derivatization‐aided strategy was developed for rapidly elucidating the structure of tramadol‐like compounds. The method is intended to assist forensic chemists in better diagnosing T and its analogs and metabolites in clinical or forensic toxicology laboratories. [ABSTRACT FROM AUTHOR]

Background: The increasing mortality and morbidity rates associated with poisoning in India have become a major public health concern. This short review paper discusses the urgent need for a comprehensive poisoning incident reporting and monitoring system to address data gaps and combat this threat at the national level. A national poisoning incident registry would not only provide traditional uses of data like aiding in the processes of planning, resource allocation, design of health programs, and public health research in the field of toxicology but also serve as a valuable tool for researchers investigating the scientific validity of using organs salvaged from poisoning cases for transplantation purposes. Discussion: With the emergence of biocrime as a stark reality in the post-COVID-19 era, the need for rigorous documentation of all poisoning incidents has become even more critical. Given the potential for molecular and genetic level threats, including bioterrorism, a strong public health surveillance system in the field of toxicology is essential in the future. Conclusion: The data on healthcare events is crucial for the proper implementation of healthcare programs, disease/issue control, and clinical decision-making. The Health Management Information System (HMIS) shows great promise in supporting decision-makers and healthcare professionals in providing high-quality care and reducing illness burden. The integration of toxicology event-related data in a registry on the lines of HMIS has a huge potential in improving the quality of health care in clinical toxicology scenarios in India. In conclusion, the implementation of a national toxicology incident registry is a categorical imperative to address the growing threat of poisoning fatalities in India.

This study reports the first application of in silico methods to assess the toxicity of 4-chloromethcathinone (4-CMC), a novel psychoactive substance (NPS). Employing advanced toxicology in silico tools, it was possible to predict crucial aspects of the toxicological profile of 4-CMC, including acute toxicity (LD50), genotoxicity, cardiotoxicity, and its potential for endocrine disruption. The obtained results indicate significant acute toxicity with species-specific variability, moderate genotoxic potential suggesting the risk of DNA damage, and a notable cardiotoxicity risk associated with hERG channel inhibition. Endocrine disruption assessment revealed a low probability of 4-CMC interacting with estrogen receptor alpha (ER-α), suggesting minimal estrogenic activity. These insights, derived from in silico studies, are critical in advancing the understanding of 4-CMC properties in forensic and clinical toxicology. These initial toxicological findings provide a foundation for future research and aid in the formulation of risk assessment and management strategies in the context of the use and abuse of NPSs. [ABSTRACT FROM AUTHOR]

Pregabalin is a gabapentinoid approved for the treatment of general anxiety disorder, neuropathic pain and as adjunctive therapy for focal seizures in patients with epilepsy. In addition, there are a number of conditions for which pregabalin is prescribed off-label. Along with the widespread use there are a significant number of reports describing the misuse of pregabalin over the last decade. Over time, it became clear that pregabalin should become part of routine testing in toxicology laboratories. The aim of this paper was to present validation of a LC-MS/MS method for the quantification of pregabalin in plasma of acutely poisoned patients. Simple sample preparation step and rapid chromatographic separation shortened the overall analysis time, which was the goal of method development. The presence of pregabalin was confirmed with three ion transitions, ensuring high selectivity of the validated method. The statistical data obtained showed good precision and accuracy over a wide concentration range. No endogenous or other interference was detected, and there was no matrix effect influence with this method. The LC-MS/MS method was applied to quantify pregabalin in plasma samples of patients admitted to the emergency department due to a possible acute pregabalin overdose. Different concentrations were found, and we report, to the best of our knowledge, the highest plasma concentration of pregabalin in the plasma of a patient with acute poisoning. In conclusion, we developed a fast and simple LC-MS/MS method for reliable determination of pregabalin and demonstrated the developed method was suitable for routine use in clinical toxicology setting. [ABSTRACT FROM AUTHOR]

Propafenone (PPF) belongs to the class 1C antiarrhythmics and can cause electrocardiogram-associated adverse/toxic effects. Cases of PPF intoxication are rarely investigated. We developed a novel and selective GC-MS/MS method for the determination of PPF and its tissue distribution in an intentional fatal poisoning case, which is applicable to PPF quantification in the range of therapeutic to lethal concentrations in complex post-mortem samples. A simple and effective sample pretreatment was applied to all analyzed samples. PPF was determined without the need for dilution, even in highly complex samples containing a wide range of analyte concentrations. Quantification was performed using the standard addition method, developed and validated according to the ICH M10 guidelines. The obtained results indicated that the PPF concentration in the serum from blood taken while alive, before therapy, was the highest ever reported in the literature. Despite the intensive therapy after the patients' admission, the PPF concentrations in the lungs, spleen, femoral blood and cardiac blood were fatal or abnormally high. On the other hand, the concentrations in the liver and skeletal muscle were lower or approximately the same as observed in cases with therapeutic doses. To the best of our knowledge, the distribution of PPF has not been investigated in fatal intoxication cases and can be helpful in clinical or forensic toxicology. [ABSTRACT FROM AUTHOR]

To prepare medical students appropriately for the management of toxicological emergencies, we have developed a simulation‐based medical education (SBME) training in acute clinical toxicology. Our aim is to report on the feasibility, evaluation and lessons learned of this training. Since 2019, each year approximately 180 fifth‐year medical students are invited to participate in the SBME training. The training consists of an interactive lecture and two SBME stations. For each station, a team of students had to perform the primary assessment and management of an intoxicated patient. After the training, the students completed a questionnaire about their experiences and confidence in clinical toxicology. Overall, the vast majority of students agreed that the training provided a fun, interactive and stimulating way to teach about clinical toxicology. Additionally, they felt more confident regarding their skills in this area. Our pilot study shows that SBME training was well‐evaluated and feasible over a longer period. [ABSTRACT FROM AUTHOR]

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Backgrounds and aims: In toxicology, LC-HRMS for untargeted screening yields a great deal of high quality spectral data. However, there we lack tools to visualize/organize the MS data. We applied molecular networking (MN) to untargeted screening interpretation. Our aims were to compare theoretical MS libraries obtained in silico with our experimental dataset in patients to broaden its application, and to use the MetWork web application for metabolite identification. Methods: Samples were analyzed using an LC-HRMS system. For MN, data was generated using MZmine, and analyzed and visualized using MetGem. MetWork annotations were filtered and this file was used for annotation of the previously obtained MN. Results: 155 compounds including drugs found in patients were recorded. Using this dataset, we confirmed in 60 patients intake of tramadol, amitriptyline bromazepam, and cocaine. The results obtained by the reference methods were confirmed by MN approaches. Eighty percent of the compounds were common to both conventional and MN approaches. Using MetWork, metabolites and parent drugs such as amitriptyline, its metabolite nortriptyline and amitriptyline glucuronide phase 2 metabolites were anticipated and proposed as putative annotations. Conclusion: The workflow increases confidence in toxicological screening by highlighting putative structures in biological matrices in combination with CFM-ID (Competitive Fragmentation Modeling for Metabolite Identification) and MetWork to extend the annotation of potential drugs even without a reference standard.

Introduction: Carbamazepine causes dose-dependent toxicity in overdose. Resources commonly state that severe toxicity occurs with ingestions >50 mg/kg without supporting evidence. We aimed to compare ingested dose with clinical toxicity. Methods: This was a retrospective series of patients reportedly ingesting carbamazepine >2,000 mg referred to a clinical toxicology unit and state poisons information centre. Medical records were reviewed to extract patient demographics, ingestion details, clinical effects and management. Severe toxicity was defined as the presence of coma (Glasgow Coma Scale <9), seizure, or hypotension (systolic blood pressure <90 mmHg). Results: There were 69 presentations in 42 patients with a median ingested carbamazepine dose of 113 mg/kg (IQR: 71–151 mg/kg). Coma occurred in 10 cases, eight having ingested >200 mg/kg and the remaining two ingesting 113 mg/kg and 151 mg/kg, respectively. Seizures occurred in four cases (lowest ingested dose 143 mg/kg). Hypotension occurred in five cases (lowest ingested dose 113 mg/kg). Discussion: Severe carbamazepine toxicity did not occur with reported ingestions <100 mg/kg and was uncommon in ingestions <200 mg/kg. Conclusion: Severe toxicity was common in ingestions >200 mg/kg. Using the suggested threshold of severe toxicity of >50 mg/kg appeared overly conservative in this series. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) will impact many aspects of clinical pharmacology, including drug discovery and development, clinical trials, personalized medicine, pharmacogenomics, pharmacovigilance and clinical toxicology. The rapid progress of AI in healthcare means clinical pharmacologists should have an understanding of AI and its implementation in clinical practice. As with any new therapy or health technology, it is imperative that AI tools are subject to robust and stringent evaluation to ensure that they enhance clinical practice in a safe and equitable manner. This review serves as an introduction to AI for the clinical pharmacologist, highlighting current applications, aspects of model development and issues surrounding evaluation and deployment. The aim of this article is to empower clinical pharmacologists to embrace and lead on the safe and effective use of AI within healthcare. [ABSTRACT FROM AUTHOR]

This paper aims to explore the possibility of employing large language models (LLMs) – a type of artificial intelligence (AI) – in clinical pharmacology, with a focus on its possible misuse in bioweapon development. Additionally, ethical considerations, legislation and potential risk reduction measures are analysed. The existing literature is reviewed to investigate the potential misuse of AI and LLMs in bioweapon creation. The search includes articles from PubMed, Scopus and Web of Science Core Collection that were identified using a specific protocol. To explore the regulatory landscape, the OECD.ai platform was used. The review highlights the dual‐use vulnerability of AI and LLMs, with a focus on bioweapon development. Subsequently, a case study is used to illustrate the potential of AI manipulation resulting in harmful substance synthesis. Existing regulations inadequately address the ethical concerns tied to AI and LLMs. Mitigation measures are proposed, including technical solutions (explainable AI), establishing ethical guidelines through collaborative efforts, and implementing policy changes to create a comprehensive regulatory framework. The integration of AI and LLMs into clinical pharmacology presents invaluable opportunities, while also introducing significant ethical and safety considerations. Addressing the dual‐use nature of AI requires robust regulations, as well as adopting a strategic approach grounded in technical solutions and ethical values following the principles of transparency, accountability and safety. Additionally, AI's potential role in developing countermeasures against novel hazardous substances is underscored. By adopting a proactive approach, the potential benefits of AI and LLMs can be fully harnessed while minimizing the associated risks. [ABSTRACT FROM AUTHOR]

When predicting future events, we often rely on analyzing past occurrences and projecting them forward. This methodology is crucial in various fields, including toxicology, in which predicting outcomes in poisoned patients plays a vital role in guiding treatment decisions and improving patient care. In cases of poisoning, understanding a patient's medical history, current physiological status, and the toxicokinetics of the ingested substance is essential for predicting potential outcomes and determining appropriate interventions. Predicting whether an intoxicated patient needs (further) treatment or even admission to the hospital is one of the most difficult decisions a clinician needs to make. The prediction of the course of an intoxication often lacks crucial information, leaving physicians with a sense of uncertainty in treating and advising patients. A significant source of this uncertainty stems from patients' limited awareness of the specific chemical(s) causing their symptoms, making a targeted approach challenging. Adding to the complexity, both patients and physicians frequently lack knowledge of the exposure dose, onset time, and potential interactions, further complicating the prediction of symptom progression. Patients are commonly placed in observation wards until the pharmacodynamic effects have diminished, leading to extended observation periods and unnecessary healthcare utilization and costs. Therefore, a key objective of a predictive model is to determine the necessity for intensive care unit admission. Factors such as age, Glasgow Coma Scale, and specific comorbidities like dysrhythmias and chronic respiratory insufficiency significantly influence the likelihood of intensive care unit admission. By examining a patient's trajectory based on past medical history and organ function deterioration, clinicians can better anticipate the need for critical care support. To enhance prediction models, leveraging modern methodologies like machine learning on large datasets (big data) are crucial. These advanced techniques can uncover previously unknown patient groups with similar outcomes or treatment responses, leading to more personalized and effective interventions. Regular updates to clustering, discrimination, and calibration processes ensure that predictive models remain accurate and relevant as new data emerges. The field of clinical toxicology stands to benefit greatly from the creation and integration of large datasets to advance toxicological prognostication. By embracing innovative approaches and incorporating diverse data sources, clinicians can enhance their ability to predict outcomes in poisoned patients and improve overall patient management strategies. [ABSTRACT FROM AUTHOR]

Introduction: Valproic acid (VPA) is a broad-spectrum drug primarily used in the treatment of epilepsy and bipolar disorder. It is not an uncommon occurrence for VPA to cause intoxication. The established treatment of VPA poisoning includes supportive care, multiple doses of activated charcoal, levocarnitine and hemodialysis/hemoperfusion. There is a clinically significant interaction between carbapenem antibiotics and VPA. By affecting enterohepatic recirculation, carbapenems can increase the overall VPA clearance from the blood of intoxicated patients. It is suggested that carbapenems could successfully be used as antidotes in the treatment of acute VPA poisonings. The aim: To evaluate the effectiveness of carbapenems in the treatment of patients acutely poisoned by VPA. Patients and methods: This retrospective study included patients acutely poisoned by VPA and treated with carbapenems at the Department of Clinical Toxicology at the Military Medicinal Academy in Serbia for a two-year period. Results: After the admission, blood concentrations of VPA kept increasing, reaching their peak at 114–724 mg/L, while the mental state of the patients continued to decline, prompting a decision to introduce carbapenems. After the introduction of carbapenems, the concentrations of the drug dropped by 46–93.59% (average 72%) followed by rapid recovery of consciousness. Ten out of eleven patients had positive outcomes, while one patient died. The most commonly observed complication in our group of patients was bronchopneumonia. Conclusions: The application of carbapenems for the management of acute VPA poisoning might be a useful and effective treatment option. [ABSTRACT FROM AUTHOR]

Kratom (Mitragyna speciosa) has generated substantial clinical and scientific interest as a complex natural product. Its predominant alkaloid mitragynine and several stereoisomers have been studied for activity in opioid, adrenergic, and serotonin receptors. While awaiting clinical trial results, the pre-clinical evidence suggests a range of potential therapeutic applications for kratom with careful consideration of potential adverse effects. The focus of this review is on the pharmacology, pharmacokinetics, and potential drug–drug interactions of kratom and its individual alkaloids. A discussion on the clinical pharmacology and toxicology of kratom is followed by a summary of user surveys and the evolving concepts of tolerance, dependence, and withdrawal associated with kratom use disorder. With the increasing use of kratom in clinical practice, clinicians should be aware of the potential benefits and adverse effects associated with kratom. While many patients may benefit from kratom use with few or no reported adverse effects, escalating dose and increased use frequency raise the risk for toxic events in the setting of polysubstance use or development of a use disorder. [ABSTRACT FROM AUTHOR]

Purpose: This study reviews the use of mirabilite in traditional Chinese medicine and various preparations by describing its chemical composition, processing methods, pharmacology, toxicology, and clinical research progress. Methods: The applications and processing methods of mirabilite are searched in traditional and modern Chinese medical writings, and the articles on chemical composition, pharmacological effects, toxicology, and clinical studies of mirabilite and its combinations in PubMed and China Knowledge Network are reviewed, sorted, and analyzed. Results: The main chemical component of mirabilite is sodium sulfate decahydrate (Na2SO4·10H2O), followed by small amounts of sodium chloride, magnesium sulfate, calcium sulfate, and other inorganic salts. This study systematically organizes the history of the medicinal use of mirabilite in China for more than 2,000 years. This mineral has been used by nine Chinese ethnic groups (Han, Dai, Kazakh, Manchu, Mongolian, Tujia, Wei, Yi, and Tibetan) in a large number of prescription preparations. The Pharmacopoeia of the People's Republic of China (2020 edition) records stated that mirabilite can be used for abdominal distension, abdominal pain, constipation, intestinal carbuncle, external treatment of breast carbuncle, hemorrhoids, and other diseases. The traditional processing methods of mirabilite in China include refining, boiling, sautéing, filtration after hot water blistering, and firing. Since the Ming Dynasty, processing by radish has become the mainstream prepared method of mirabilite. Mirabilite can exhibit antiinflammatory detumescence effects by inhibiting AMS, LPS, IL-6, IL-10, TNF-α, and NO levels and attenuating the upregulation of TNF-α and NF-κB genes. It can promote cell proliferation and wound healing by increasing the production of cytokines TGFβ1 and VEGF-A and gastrointestinal motility by increasing the release of vasoactive intestinal peptide, substance P, and motilin. It can increase the expression of low-density lipoprotein receptor and AKT phosphorylation in the liver by up-regulating bile acid synthesis genes; reduce TRB3 expression in the liver, FGF15 co-receptor KLB expression, and FGF15 production in the ileum, and JNK signal transduction; and increase the transcription of CYP7A1 to achieve a cholesterol-lowering effect. Mirabilite also has a variety of pharmacological effects, such as regulating intestinal flora, anti-muscle paralysis, anti-colon cancer, promoting water discharge, and analgesic. Only a few toxicological studies on mirabilite are available. External application of mirabilite can cause local skin to be flushed or itchy, and its oral administration is toxic to neuromuscular cells. The sulfur ions of its metabolites can also be toxic to the human body. At present, no pharmacokinetic study has been conducted on mirabilite as a single drug. This mineral has been widely used in the clinical treatment of inflammation, edema, wound healing, digestive system diseases, infusion extravasation, hemorrhoids, skin diseases, breast accumulation, muscle paralysis, intestinal preparation before microscopic examination, and other diseases and symptoms. Conclusion: Mirabilite has good application prospects in traditional Chinese medicine and ethnomedicine. In-depth research on its processing methods, active ingredients, quality control, pharmacokinetics, pharmacological and toxicological mechanisms, and standardized clinical application is needed. This paper provides a reference for the application and research of mirabilite in the future. [ABSTRACT FROM AUTHOR]

The article discusses the use of nalmefene as an alternative treatment for opioid overdose. Nalmefene is an opioid antagonist that was recently approved by the US FDA for emergency treatment of opioid overdose. However, the article argues that nalmefene should not replace naloxone as the primary opioid antidote at this time. The authors express concerns about the lack of clinical data supporting the effectiveness and safety of nalmefene, as well as the potential for longer-lasting withdrawal symptoms and the need for extended medical observation. They recommend further clinical studies and comparative studies with naloxone to determine the differences in effectiveness and adverse outcomes. [Extracted from the article]

Background: Gender diversity in both emergency medicine and medical toxicology has grown over the last decade. However, disparities in promotion, awards, and speakership still exist. No studies have examined gender disparities in authorship in medical toxicology journals. Research Questions: Does the proportion of female first authors and female senior authors in medical toxicology publications increase over time? What factors predict female authorship in the first author or last author positions in two major medical toxicology journals? Methods: We performed a retrospective review of all non-abstract publications in two medical toxicology journals, Clinical Toxicology and Journal of Medical Toxicology, between 2011 and 2020. We collected author names, number of authors, publication type, and publication year. Author names were used to identify author gender using Gender-API integrative tool. Data on the percentages of female medical toxicology fellows and medical toxicologists was provided by the American Board of Emergency Medicine (ABEM). Results: A total of 2212 publications were reviewed and 2171 (97.9%) were included in the dataset. Overall, 31.7% of first authors were identified as female and 67.0% were identified as male by the Gender-API tool. There were 46.8% male-male author dyads, 24.2% female-male author dyads, 12.1% male-female author dyads, and 5.7% female-female author dyads. Predictors of female first authorship included research and case report articles, and percentage of ABEM female toxicologists. Predictors of female senior authorship included number of authors and percentage of ABEM female toxicologists. The proportion of female authorship in both categories increased over the study period. Conclusions: The frequency of female authorship in the first author position has grown over the last decade and is associated with increasing female representation in medical toxicology and specific manuscript subtypes, specifically research manuscripts. [ABSTRACT FROM AUTHOR]

The document titled "Acknowledgement of reviewers" is a list of scientists who have reviewed articles for the journal Basic & Clinical Pharmacology & Toxicology from 2022 to 2023. The list includes scientists from different countries and backgrounds, highlighting the diversity of expertise in the field of pharmacology and toxicology. This document serves as a recognition of their contributions to the journal and their valuable insights in the field. [Extracted from the article]

Background: Liquid chromatography-high-resolution mass spectrometry (LC-HR-MS) has emerged as a powerful analytical technology for compound screening in clinical toxicology. To evaluate the potential of LC-HR-MS3 in detecting toxic natural products, a spectral library of 85 natural products (79 alkaloids) that contains both MS2 and MS3 mass spectra was constructed and used to identify the natural products. Samples were analyzed using an LC-HR-MS3 method and the generated data were matched to the spectral library to identify the natural products. Methods: To test the performance of the LC-HR-MS3 method in different sample matrices, the 85 natural product standards were divided into three groups to separate structural isomers and avoid ion suppression effects caused by co-elution of multiple analytes. The grouped analytes were spiked into drug-free serum and drug-free urine to produce contrived clinical samples. Results: The compound identification results of the 85 natural products in urine and serum samples were obtained. The match scores using both MS2 and MS3 mass spectra and those using only MS2 mass spectra were compared at 10 different analyte concentrations. The two types of data analysis provided identical identification results for the majority of the analytes (96% in serum, 92% in urine), whereas, for the remaining analytes, the MS2-MS3 tree data analysis had better performance in identifying them at lower concentrations. Conclusion: This study shows that in comparison to LC-HR-MS (MS2), LC-HR-MS3 can increase the performance in identification of a small group of the toxic natural products tested in serum and urine specimens.

This document provides abstracts from studies presented at the Middle East and North Africa Clinical Toxicology Association Meeting in Abu Dhabi. The studies cover a range of topics, including the presence of warning labels on energy drinks in Kuwait, snakebites in Saudi Arabia, the efficacy of high-dose Methylprednisolone in preventing esophageal stricture formation, medical toxicology knowledge in Oman, and patterns of telephone enquiries related to suicide attempts in Sudan. The document also includes case reports of toxic exposures and poisonings, highlighting the importance of recognizing toxic exposures and providing appropriate treatment. Additionally, there are cases discussing different types of poisonings and their treatment, including colchicine overdose, radiation emergencies, envenomation medical care in zoos, monitoring viperine venom-induced consumptive coagulopathy, and the economic impact of managing paracetamol poisoning in Algeria. These cases underscore the significance of proper treatment and preparedness in handling various types of poisonings. [Extracted from the article]

In response to the alarming rates of zolpidem abuse, this study presents a pioneering approach utilizing molecularly imprinted nanoparticles (MIPs) in conjunction with high‐performance liquid chromatography (HPLC) for the selective detection of zolpidem. The rational choice of zolpidem as the target analyte stems from its widespread misuse and clinical significance. The MIPs were prepared using the precipitation polymerization method, resulting in monodispersed nanoparticles with a size of approximately 258.8 nm. Fourier Transform Infrared (FTIR) analysis confirmed the successful incorporation of zolpidem into the MIPs, designed with tailored cavities for zolpidem recognition. Moreover, incorporating the bathochromic shift phenomenon reaffirms the successful imprinting procedure. The rebinding studies showed that MIPs were highly efficient in adsorbing zolpidem from the solvent, with more than 95 % of the drug recovered after multiple cycles. The selectivity study demonstrated the MIPs′ preference for zolpidem over another drug, diazepam. The MIPs′ successful separation of zolpidem from spiked human plasma samples further validates their potential for practical applications, such as clinical toxicology. This research showcases the potential of MIPs coupled with HPLC as a powerful tool for accurate zolpidem quantification, holding great promise for combating drug abuse and advancing analytical methodologies for pharmaceutical analysis. [ABSTRACT FROM AUTHOR]

The use of medicines during pregnancy is a growing public health concern due to the risk of developmental toxicity. Healthcare providers heavily rely on the FDA pregnancy risk categories (A, B, C, D, and X). Antibiotics are among the most prescribed drugs during pregnancy and are often listed under category B or C. However, the risk-benefit assessment may be lacking due to challenges in the clinical toxicology studies on pregnant women, such as ethical concerns. The primary focus of this study is to generate a model that predicts the safe use of antibiotics during pregnancy by using in silico approaches. Thus, a QSAR model was created to assess the FDA pregnancy category (B or C) of antibiotics. The dataset consisted of 97 antibiotics obtained from the FDA. A total of 6420 molecular descriptors were determined via multiple software and various machine learning algorithms were utilized. The performance of the models was measured using internal and external validation. The accuracy (ACC) values of the most successful model were 83.82% for the internal and 94.11% for the external validation. Sensitivity (SE), specificity (SP), MCC, and ROC values were 0.878, 0.778, 0.68, and 0.892 for the internal validation and 0.9, 1, 0.887, and 0.936 for the external validation, respectively. Kappa statistics also indicate that there was a substantial agreement for internal validation with 0.6765 and an almost perfect agreement for external validation with 0.8811. In conclusion, our model can be used as an initial step before pre-clinical and clinical studies to predict the safe use of antibiotics in pregnancy. [ABSTRACT FROM AUTHOR]

Stonefish envenomation results in localized severe pain and swelling and systemic features, including vomiting, arrhythmia, pulmonary oedema, and possibly death. There are limited data regarding the effectiveness of the available antivenom. The aim of this series is to characterize presentations of patients with suspected stonefish envenomation and investigate treatment, including antivenom. This is a retrospective observational series of suspected stonefish envenomation as reported to the Queensland Poisons Information Centre or Princess Alexandra Hospital Clinical Toxicology Unit from July 2015 to January 2023. Patients were identified through the databases held by both the Centre and Unit, and data on clinical features and investigations were collected from the patient's electronic medical record. There were 87 suspected stonefish envenomations from July 2015 to January 2023. The median age was 26 (range: 5-69) years, and 69 (79 per cent) patients were male. Pain was reported in 85 (98 per cent) with a median peak pain score of 10 (range 4-12; three rated their pain greater than 10/10). A clear wound was documented in 64 (74 per cent), with local swelling in 63 (72 per cent). A foreign body was retained in eight (9 per cent) presentations. Systemic symptoms were rare, with vomiting in four (5 per cent) and dizziness in two (2 per cent) presentations. There were no instances of hypotension, arrhythmia, or pulmonary oedema. Hot water was administered in 72 (83 per cent) presentations. Oral analgesia was given in 55 (63 per cent). Parenteral analgesia was given in 53 (61 per cent), most commonly opioids. Local anaesthetic block was performed in 19 presentations (22 per cent), with effectiveness documented in 16/19 (84 per cent). Five patients received antivenom for intractable pain, and all received subsequent parenteral analgesia or local anaesthetic block. Stonefish envenomation is characterized by severe pain. Systemic symptoms were rare and not severe in this series. Local anaesthetic block appeared to be the most effective intervention for severe pain when performed. Antivenom appeared to be ineffective in managing pain. [ABSTRACT FROM AUTHOR]

Nalmefene is a potent opioid antagonist that has recently been reintroduced in the United States to treat known or suspected opioid overdose. The injection formulation, which had been withdrawn in 2008, was reintroduced in 2022, and in 2023 the United States Food and Drug Administration approved a new intranasal formulation of nalmefene. Because nalmefene had been previously approved for use in 1995 via injection, the new intranasal formulation did not require new clinical data as it was approved under an Abbreviated New Drug Application. Inherent to this abbreviated approval process, intranasal nalmefene was not studied in patients currently suffering opioid overdose. Nalmefene also has unique characteristics compared with naloxone, the current standard opioid antidote. Nalmefene has a higher affinity for opioid receptors and a longer duration of action than naloxone. Comparative effectiveness data regarding naloxone and nalmefene are sparse, and it is unclear if the inherent properties of nalmefene are beneficial in opioid overdose. We have decades of experience using naloxone safely and effectively as the primary opioid antidote, even in cases of fentanyl and fentanyl analog overdoses. There is, however, evidence to suggest nalmefene may result in more prolonged and severe opioid withdrawal than naloxone, which could be harmful to patients. As nalmefene is untested in the current clinical environment of synthetic opioid overdoses and has the potential to cause harm via prolonged withdrawal, it is the opinion of the American College of Medical Toxicology and the American Academy of Clinical Toxicology that nalmefene should not replace naloxone as the primary opioid antidote at this time. We recommend additional clinical studies of nalmefene, administered via all approved routes, be conducted in a comparative fashion with naloxone, and that safety and effectiveness outcomes be evaluated before nalmefene is recommended as a primary opioid antidote. [ABSTRACT FROM AUTHOR]

Background: A consensus guideline on salicylate poisoning recommends referring patients to the emergency department if they ingested 150 mg/kg of aspirin. The dose of aspirin associated with severe poisoning in pediatric patients has not been investigated. Objective: This study aims to associate medical outcomes with aspirin overdoses in patients 5 years old and younger. Methods: A retrospective review of data on pediatric patients with single substance aspirin exposures reported from poison centers across the country was conducted. The primary endpoint was to associate aspirin doses with medical outcomes. Secondary endpoints included evaluation of the signs, symptoms, and treatments of ingestion and their association with medical outcomes. Results: There were 26 488 included exposures with aspirin exposures resulting in no effect (92.5%), minor effect (6.0%), moderate effect (1.4%), major effect (0.2%), and death (0.02%). There were 8921 cases with available weight-based dosing information. Median doses associated with no effect, minor effects, moderate effects, major effects, and death ranged between 28.4 and 40.9 mg/kg, 52.5 and 82.3 mg/kg, 132.1 and 182.3 mg/kg, 132.3 and 172.8 mg/kg, and 142.2 and 284.4 mg/kg, respectively. Minor effect and moderate effect exposures were more likely to have alkalinization documented compared to no effect exposures (odds ratio [OR] = 1.75, 95% confidence interval [CI] = 1.41-2.17; OR = 1.79, 95% CI = 1.12-2.86). There was no difference in rates of alkalinization between minor and moderate exposures (OR = 1.02, 95% CI: 0.61-1.7). Conclusions and relevance: Reevaluation of the current recommendation of 150 mg/kg for referral to a healthcare facility is necessary for pediatric acute salicylate overdoses. [ABSTRACT FROM AUTHOR]

This article discusses the emergence of a new synthetic cathinone called dipentylone in Spain's illicit drug landscape. Synthetic cathinones are being marketed as replacements for amphetamine-derivatives and are often mislabeled as MDMA or used as adulterants. Dipentylone is a stimulant with effects similar to amphetamine and is twice as potent at inhibiting dopamine uptake as cocaine or MDMA. The article presents two cases of patients who unknowingly consumed dipentylone and experienced adverse effects. The study highlights the importance of comprehensive toxicological analysis to identify substances involved in acute drug intoxications. [Extracted from the article]

The article discusses the importance of Letters to the Editor (LTEs) in facilitating scientific discourse and serving as a forum for public discussion. It acknowledges the rise of informal scientific writing on social media but argues that LTEs remain valuable for critiquing and expanding scholarly work. The article highlights the limitations of social media in disseminating accurate information and emphasizes the need for professionalism and fact-checking in LTEs. It provides guidance on writing effective LTEs, including adhering to specific instructions and focusing on specific points. The article also encourages submissions to the Poison Pen section of the Journal of Medical Toxicology, which publishes letters related to recent articles and contemporary issues in medical toxicology. It emphasizes the importance of clear and accurate writing and encourages authors of all levels to submit LTEs. The article concludes by inviting readers to engage in post-publication peer review and contribute to the intellectual forum of scientific enterprise. [Extracted from the article]

The article is a welcome message from the journal Basic & Clinical Pharmacology & Toxicology for the year 2024. It highlights the publication of three Special Collections from conferences supported by the Nordic Association for the Publication of Basic and Clinical Pharmacology and Toxicology. The journal also announces the BCPT Young Investigator's Award for 2023 and the establishment of a new virtual Annual Special Collection for young investigators. In addition, the article mentions the appointment of Editor's choice articles and the promotion of content on social media platforms. The revenue generated by the journal is used to support scientific meetings and events in the Nordic countries. The article concludes by expressing gratitude to readers, contributors, reviewers, and the editorial team, and emphasizes the journal's commitment to scientific rigor in publishing original studies. [Extracted from the article]

Background and objectives: Aluminum phosphide (AlP), known as “rice tablet,” is widely used as an effective pesticide. However, AlP poisoning is a common cause of mortality in many countries, such as Iran. Unfortunately, there is no specific antidote for AlP toxicity to date. AlP releases phosphine gas when it is exposed to moisture or acid. Phosphine is a potent mitochondrial toxin that could significantly inhibit cellular energy metabolism. AlP poisoning is an emergency condition that needs instant and effective intervention. Dihydroxyacetone (DHA) is a simple saccharide used for several pharmacological as well as cosmetic purposes. Previously, we found that DHA could significantly prevent mitochondrial impairment induced by toxic agents such as cyanide and phosphine in various in vitro and in vivo experimental models. Methods: Hospitalized patients (n = 111) were evaluated for eligibility criteria. Among these patients, n = 35 cases were excluded due to incomplete data (n = 11) and suspicion of poisoning with poisons other than AlP (n = 24). Meanwhile, n = 76 cases with confirmed AlP poisoning were included in the study. AlP-poisoned patients who did not receive DHA (n = 18) were used as the control group.Patients (n = 58) received at least one dose of DHA (500 ml of 5 % DHA solution w/v, i.v.) as an adjuvant therapy in addition to the routine treatment of AlP poisoning. Arterial blood gas (ABG), blood pH, bicarbonate levels, and other vital signs and biochemical measurements were monitored. Moreover, the mortality rate and hospitalization time were evaluated in DHA-treated and AlP-poisoned patients without DHA administration. Several biomarkers were assessed before (upon hospitalization) and after DHA treatment. The routine tests for AlP-poisoned patients in this study were the measurement of electrolytes (K+ and Na+), WBC, RBC, hemoglobin, INR, carbonate (HCO3), blood pH, PaCO2, and PaO2 and SGPT, SGOT, BUN, Cr. Results: Upon patients' admission, significant decreases in blood pH (acidosis), blood PaO2, and HCO3 levels were the hallmarks of AlP poisoning. It was found that DHA significantly alleviated biomarkers of AlP poisoning and tremendously enhanced patients’ survival rate (65.52 % in DHA-treated vs 33.34 % in the control group) compared to patients treated based on hospital routine AlP poisoning protocols (no DHA). No significant adverse effects were evident in DHA-treated patients in the current study. Interpretation and conclusions: These data suggest that parenteral DHA is a novel and effective antidote against AlP poisoning to be used as an adjuvant in addition to routine supportive treatment. Trial registration: IR.SUMS.REC.1394.102.

In many countries, adherence testing is used to monitor consumption behavior or to prove abstinence. Urine and hair are most commonly used, although other biological fluids are available. Positive test results are usually associated with serious legal or economic consequences. Therefore, various sample manipulation and adulteration strategies are used to circumvent such a positive result. In these critical review articles on sample adulteration of urine (part A) and hair samples (part B) in the context of clinical and forensic toxicology, recent trends and strategies to improve sample adulteration and manipulation testing published in the past 10 years are described and discussed. Typical manipulation and adulteration strategies include undercutting the limits of detection/cut-off by dilution, substitution, and adulteration. New or alternative strategies for detecting sample manipulation attempts can be generally divided into improved detection of established urine validity markers and direct and indirect techniques or approaches to screening for new adulteration markers. In this part A of the review article, we focused on urine samples, where the focus in recent years has been on new (in)direct substitution markers, particularly for synthetic (fake) urine. Despite various and promising advances in detecting manipulation, it remains a challenge in clinical and forensic toxicology, and simple, reliable, specific, and objective markers/techniques are still lacking, for example, for synthetic urine. [ABSTRACT FROM AUTHOR]

As a continuation of part A, focusing on advances in testing for sample manipulation of urine samples in clinical and forensic toxicology, part B of the review article relates to hair, another commonly used matrix for abstinence control testing. Similar to urine manipulation, relevant strategies to manipulate a hair test are lowering drug concentrations in hair to undercut the limits of detection/cut-offs, for instance, by forced washout effects or adulteration. However, distinguishing between usual, common cosmetic hair treatment and deliberate manipulation to circumvent a positive drug test is often impossible. Nevertheless, the identification of cosmetic hair treatment is very relevant in the context of hair testing and interpretation of hair analysis results. Newly evaluated techniques or elucidation of specific biomarkers to unravel adulteration or cosmetic treatment often focused on specific structures of the hair matrix with promising strategies recently proposed for daily routine work. Identification of other approaches, e.g., forced hair-washing procedures, still remains a challenge in clinical and forensic toxicology. [ABSTRACT FROM AUTHOR]

Poisoning and overdose are very important aspects in medicine and toxicology. Chemical weapons pose a threat to civilians, and emergency medicine principles must be followed when dealing with patients who have been poisoned or overdosed. Antidotes have been used for centuries and modern research has led to the development of new antidotes that can accelerate the elimination of toxins from the body. Although some antidotes have become less relevant due to modern intensive care techniques, they can still save lives or reduce the severity of toxicity. The availability of antidotes is crucial, especially in developing countries where intensive care facilities may be limited. This article aims to provide information on specific antidotes, their recommended uses, and potential risks and new uses. In the case of poisoning, supportive therapies are most often used; however, in many cases, the administration of an appropriate antidote saves the patient's life. In this review, we reviewed the literature on selected antidotes used in the treatment of poisonings. We also characterised the antidotes (bio)chemically. We described the cases in which they are used together with the dosage recommendations. We also analysed the mechanisms of action. In addition, we described alternative methods of using a given substance as a drug, an example of which is N-acetylcysteine, which can be used in the treatment of COVID-19. This article was written as part of the implementation of the project of the Polish Ministry of Education and Science, "Toxicovigilance, poisoning prevention, and first aid in poisoning with xenobiotics of current clinical importance in Poland", grant number SKN/SP/570184/2023. [ABSTRACT FROM AUTHOR]

Hospital-treated intentional self-poisoning is common. The possibility of changed (increased) suicidal behaviors during the COVID-19 pandemic has been raised. To compare frequencies in self-poisoning events (SPEs) and the proportions with in-hospital mortality, in the year prior to and following the official onset of the COVID-19 pandemic, in a population of hospital-treated self-poisoning patients in Iran. All self-poisoned patients admitted to Loghman-Hakim Hospital, a clinical toxicology specialty hospital in Tehran, were included. The frequency of SPEs was compared between the one-year periods immediately before and after the onset of COVID-19 pandemic using Poisson regression. Differences in proportions of in-hospital mortality were also compared using logistic regression. A total of 14,478 patients with 15,391 SPEs (8,863 [61.2%] females) were evaluated in the study. There was no difference in the overall frequency of SPEs (relative risk [RR] of 0.99 [CI95% 0.96–1.03]), but a small increase in males (RR 1.07; 1.02–1.13) and a minor decrease in females (RR 0.95; 0.91–0.99). In total, 330 patients died (2.3% of all SPEs). There was no difference in overall in-hospital mortality odds ratio (OR: 0.98 [0.79–1.22]), in females (OR = 1.14 [0.80–1.60]) or males (OR = 0.92 [0.69–1.23]). There was no change in the frequency of SPEs and no difference in the in-hospital mortality proportions, suggesting that the COVID-19 pandemic had little or no effect on these aspects of suicidal behavior in Iran. [ABSTRACT FROM AUTHOR]

Immunoassay tests are used in clinical and forensic toxicology laboratories to determine illicit drug use in biological samples. Therefore, this study aims to optimize the cutoff concentrations of DOA I Plus in the blood and compare the LC-MS/MS results. 680 authentic forensic whole blood specimens with Randox Evidence DOA I Plus array were screened for drug of abuse and confirmed by LC-MS/MS. Regarding the manufacturer recommended threshold values, 139 out of 680 authentic blood samples were positive for one or more analytes, while 541 were negative. Nearly all of the 139 positive blood samples confirmed by LC-MS/MS were true positive for one or more analytes, while 522 of the 541 negative blood samples were true negative. The overall sensitivity and the specificity were 87.8% and 99.6%, respectively. THC was considered in detail, and a receiver operator characteristic curve analysis was performed to determine the optimum cutoff for THC, as it accounts for 78% of all positive results according to the manufacturer's recommended thresholds. The optimal threshold value for THC was determined at a concentration of 23 ng/mL, while these values for other parameters were defined as recommended by the manufacturer. [ABSTRACT FROM AUTHOR]

In conventional clinical toxicology practice, the blood level of carboxyhemoglobin is a biomarker of carbon monoxide (CO) poisoning but does not correspond to the complete clinical picture and the severity of the poisoning. Taking into account articles suggesting the relationship between oxidative stress parameters and CO poisoning, it seems reasonable to consider this topic more broadly, including experimental biochemical data (oxidative stress parameters) and patients poisoned with CO. This article aimed to critically assess oxidative-stress-related parameters as potential biomarkers to evaluate the severity of CO poisoning and their possible role in the decision to treat. The critically set parameters were antioxidative, including catalase, 2,2-diphenyl-1-picryl-hydrazyl, glutathione, thiol and carbonyl groups. Our preliminary studies involved patients (n = 82) admitted to the Toxicology Clinical Department of the University Hospital of Jagiellonian University Medical College (Kraków, Poland) during 2015–2020. The poisoning was diagnosed based on medical history, clinical symptoms, and carboxyhemoglobin blood level. Blood samples for carboxyhemoglobin and antioxidative parameters were collected immediately after admission to the emergency department. To evaluate the severity of the poisoning, the Pach scale was applied. The final analysis included a significant decrease in catalase activity and a reduction in glutathione level in all poisoned patients based on the severity of the Pach scale: I°–III° compared to the control group. It follows from the experimental data that the poisoned patients had a significant increase in level due to thiol groups and the 2,2-diphenyl-1-picryl-hydrazyl radical, with no significant differences according to the severity of poisoning. The catalase-to-glutathione and thiol-to-glutathione ratios showed the most important differences between the poisoned patients and the control group, with a significant increase in the poisoned group. The ratios did not differentiate the severity of the poisoning. The carbonyl level was highest in the control group compared to the poisoned group but was not statistically significant. Our critical assessment shows that using oxidative-stress-related parameters to evaluate the severity of CO poisoning, the outcome, and treatment options is challenging. [ABSTRACT FROM AUTHOR]