Clinical Toxicology最新文献

Introduction: Carbon monoxide poisoning may result in various neurological injuries, including acute symptomatic seizures. We aimed to investigate the long-term risk of epilepsy and status epilepticus in patients with previous carbon monoxide poisoning.

Methods: The study population was derived from the National Health Insurance Service database of the Republic of Korea between 1 January 2002 and 31 December 2021. We included adults with at least one documented visit to medical facilities because of carbon monoxide poisoning (International Classification of Diseases, Tenth Revision, code T58). Patients were matched, on the same index date, with controls, without a T58 code, for age, sex, insurance type, income level, and residence location in a 1:1 ratio. Follow-up continued until death, migration, or the end of the observation period (31 December 2021). The primary outcome was the incidence of epilepsy (codes G40 or R56) and status epilepticus (code G41).

Results: This study included 53,380 patients with carbon monoxide poisoning and 53,380 controls, with 44.2% women and a mean age of 45.7 years. The mean (±SD) follow-up period was 5.7 ± 4.3 years in the carbon monoxide poisoned group and 6.4 ± 4.4 years in controls. The overall risk of epilepsy (adjusted hazard ratio 2.60; 95% CI: 2.43-2.78; P <0.001) and status epilepticus (adjusted hazard ratio 4.10; 95% CI: 2.84-5.92; P <0.001) was significantly increased in the carbon monoxide poisoned group compared to controls. The risk of epilepsy and status epilepticus was increased in patients with previous carbon monoxide poisoning, regardless of sex, age or a history of stroke, neurodegenerative diseases, or central nervous system tumour or infection. However, in the subgroup analysis according to age, the highest risk of epilepsy and status epilepticus was observed in patients less than 40 years of age.

Discussion: In this population-based cohort study, previous carbon monoxide poisoning was associated with an increased risk of epilepsy and status epilepticus. The risk was more noticeable in patients aged less than 40 years. Further studies are needed to confirm such an association in other populations.

Conclusions: Previous carbon monoxide poisoning was associated with an increased risk of epilepsy and status epilepticus, particularly in the younger population. The long-term management of survivors of carbon monoxide poisoning should include monitoring for epilepsy and status epilepticus.

Introduction: The increasing presence of counterfeit opioid drugs in the United States can contaminate data collection systems and confound estimates derived from surveillance of the opioid epidemic. Data sources and analyses that can quantify the contribution of counterfeit opioid products are needed to provide accurate and timely data to inform public health responses. We describe a novel approach to identify and quantify intentional abuse and misuse exposures involving suspected counterfeit opioid products in United States poison center data.

Methods: An ecological study was performed using data, including narrative case notes, reported to participating United States Poison Centers of the Researched Abuse, Diversion and Addiction Related Surveillance System between 2009-Quarter 1 and 2021-Quarter 4. A machine learning natural language processing approach was used to develop a predictive model.

Results: Sensitivity for detecting suspected non-counterfeit-involved exposures by the predictive model was 92%, specificity was 73%, and the area under the receiver operating characteristic curve was 92%. Overall, only 2.1% of intentional abuse and misuse exposure calls were predicted to be suspected counterfeit-involved during 2009-2021; however, we observed an exponential increase in suspected counterfeit exposures over this time period. There was a 7-fold increase in the estimated number of suspected counterfeit exposures from 2009 to 2021, and 23.7% of all opioid analgesic intentional abuse and misuse exposures were suspected counterfeit-involved in 2021.

Discussion: We demonstrate the feasibility and reliability of using machine learning natural language processing to identify exposures involving suspected counterfeit opioid products in United States poison center data. Results suggest that suspected counterfeits have had a meaningful influence on rates of intentional abuse exposures to opioid analgesics in more recent years.

Conclusions: The increasing presence of counterfeit opioid drugs can contaminate data collection systems and compromise the reliability of the data.

Introduction: In 2015, Australia and New Zealand treatment guidelines recommended a 2 h paracetamol serum concentration for risk assessment of unintentional paracetamol liquid exposures. We assess our experience with this approach.

Methods: Retrospective case review of children <6 years-old with liquid paracetamol overdoses referred to a regional poisons information centre January 2017 to August 2022. We extracted data on the exposure and management from the poisons information centre and hospital medical records. We identified additional cases with two paracetamol concentrations obtained from September 2022 to June 2024.

Results: Of 437 paediatric poisonings, 271 were eligible for inclusion. The median age was 24 months, the median time to presentation was 120 min, and paracetamol was the sole ingestant in 92% of cases. Blood testing was recommended in 131 patients (48.3%), occurring at 2 h post-ingestion in 62 patients (47.3%). Testing at a later time was mostly due to delayed presentation, including to hospitals unable to measure paracetamol concentrations. Eighteen patients (16.7%) had repeat blood testing, and five additional cases were identified in the subsequent period. Overall, the concentration decreased in 19 patients (83%), but in three patients it increased, from 73 mg/L to 81 mg/L (0.49-0.54 mmol/L), from 154 mg/L to 179 mg/L (1.03-1.19 mmol/L), and from 56 mg/L to 115 mg/L (0.37-0.77 mmol/L). Symptomatic patients were more likely to receive a second blood test or acetylcysteine while awaiting investigations. Of 19 patients administered acetylcysteine, it was discontinued in five due to low paracetamol serum concentrations. All patients recovered.

Discussion: Guidelines were followed in >90% of patients and this testing regimen shortened length of stay. Based on these data, Australian treatment guidelines now recommend repeat testing for 2 h paracetamol serum concentrations >100 mg/L (0.67 mmol/L).

Conclusion: A paracetamol serum concentration between 2 h and 4 h post-ingestion in children <6 years-old with unintentional poisonings of paracetamol liquid can facilitate medical discharge.

Introduction: While factors like high serum paracetamol (acetaminophen) concentration and delayed acetylcysteine treatment increase hepatotoxicity risk, existing predictive tools, such as the paracetamol concentration aminotransferase activity multiplication product and the psi (ψ) parameter, lack definitive accuracy. This study evaluated the paracetamol psi parameter multiplication product addition against the psi parameter and the paracetamol concentration aminotransferase activity multiplication product for predicting hepatotoxicity following an acute paracetamol overdose.

Methods: A retrospective analysis of patients with acute paracetamol overdose from January 2007 to December 2016 was conducted. The paracetamol psi parameter multiplication product addition, calculated by summing the psi parameter (mmol/L × h) and the paracetamol concentration aminotransferase activity multiplication product (g U/L²), was used. Hepatotoxicity was defined as aspartate or alanine aminotransferase activities ≥1,000 U/L. Diagnostic accuracy was assessed through sensitivity, specificity, the area under the receiver operating characteristic curve, and their corresponding 95% CI, with the optimal cutoff determined using the maximum Youden index method.

Results: The study comprised 421 patients, mostly female (82.9%) with a median age of 23 years. Hepatotoxicity occurred in 13.5% (57 patients). The paracetamol psi parameter multiplication product addition showed an area under the receiver operating characteristic curve of 0.989 (95% CI: 0.974-0.997), with an optimal cutoff at 9.723, providing 96.5% sensitivity and 97.3% specificity. The paracetamol psi parameter multiplication product addition demonstrated superior performance in area under the receiver operating characteristic curve compared to the individual assessments of the psi parameter (0.916; 95% CI: 0.885-0.941) and the paracetamol concentration aminotransferase activity multiplication product (0.901; 95% CI: 0.868-0.928).

Discussion: The paracetamol psi parameter multiplication product addition appears to be a more effective diagnostic tool than the psi parameter or the paracetamol concentration aminotransferase activity multiplication product alone.

Conclusion: Incorporating the paracetamol psi parameter multiplication product addition into clinical protocols could improve paracetamol overdose management by enabling precise identification of individuals at heightened risk for hepatotoxicity, thereby facilitating the customization of treatment approaches.

Introduction: The objective of this study was to update and expand on previous studies of opioid exposures among young children reported to America's Poison Centers®, and to describe how fentanyl and medications for opioid use disorder have contributed.

Methods: This retrospective study investigated 34,632 reports of single-substance opioid exposure from 2016 to 2023 involving pediatric patients aged one month to six years old. Descriptive statistics, tests for data normality, and significance testing were performed where applicable.

Results: Of 34,632 reported exposures, 96.7% were unintentional. The median age of exposure was 2.0 years (IQR 1.33-3.0 years). Reported exposures decreased by 57.5% over the study period (r = -0.96; P <0.001). However, there was a 300% absolute increase in deaths and major effects (r = 0.96; P <0.001). Exposures resulting in minor, no effect, not followed, or unable to follow decreased 66.2% (r = -0.99; P <0.001). Buprenorphine was most frequently involved, comprising 23.4% of reported exposures. Buprenorphine (OR 1.93; P <0.001) and methadone (OR 14.98; P <0.001) were associated with an increased risk of severe effects when compared to other prescription drugs (OR: 1). There was an absolute increase of 512% over time in reports of heroin, fentanyl, synthetic non-pharmaceutical opioids (r = 0.92; P <0.001), which were also associated with severe effects (OR 20.1; P <0.001).

Discussion: Pediatric opioid exposures have previously been reported to be relatively stable. It is likely the 57.5% reduction is exaggerated due to underreporting from health care providers. However, decreases in exposures are presumed to be balanced throughout the dataset and, therefore, without differential impact on other points of analysis. Our study highlights the continued need for enhanced poisoning prevention strategies.

Conclusions: The relative severity of poisonings reported to poison centers worsened over the study period. The opioids implicated have shifted away from hydrocodone, oxycodone, and tramadol, and towards fentanyl and buprenorphine.

Introduction: Clinicians managing patients with acute recreational drug or new psychoactive substance toxicity typically depend on self-reported drug(s) used. This study compares patient self-report (and/or from other sources) to the substance(s) that were subsequently identified in serum.

Methods: A prospective sample of 1,000 adults presenting to a tertiary care, urban emergency department in London, United Kingdom, with acute recreational drug/new psychoactive substance toxicity was collected from 1 February 2019 to 2 February 2020. A total of 939 appropriate samples underwent qualitative analysis by high-resolution mass spectrometry with comparison to a database of drugs/metabolites. Data on the stated drug(s) used were extracted from the routine medical chart/records; results were batched by drug class, when appropriate, and analysis was performed using R software.

Results: Seven hundred and ninety-nine (85.1%) patients were male with a median (IQR) age of 34 years (27 to 42 years). Six hundred and thirty-five (67.6%) patients reported using two or more drugs. The median (IQR) positive predictive value of a self-report substance having been taken was 0.68 (IQR: 0.44-0.86); conversely, the median negative predictive value of a substance having not been taken was 0.90 (IQR: 0.53-0.95). There was variability in the accuracy of reporting. For example, self-reported opioid use had a 90.5% likelihood that opioids were detected on analysis, whereas hallucinogens were only detected in 18.8% of samples when use was reported. Individuals were also mostly accurate in not underreporting substances. For example, those not explicitly reporting gamma-hydroxybutyrate use were 97.5% truly negative.

Discussion: Overall, most users were relatively accurate in their self-report of what class of drugs they had used, although there was variability in this accuracy. However, other drugs were present even when not reported, for example, opioids with disproportionate detection of prescription and over-the-counter (non-prescription) opioids that were unreported.

Conclusions: Self-report (and/or collateral reports) had overall relatively high concordance with the likelihood that a substance was, or was not, recently used. Therefore, clinicians can make initial treatment decisions based on the self-reported drug(s) used in most cases.

Introduction: To the best of our knowledge, clinically significant endogenous ethylene glycol production has never been reported in humans, very seldom reported in other animals or microorganisms, and then only under rare and specific conditions. We describe the detailed investigations we undertook in two adult monozygotic twin sisters to ascertain whether they were producing endogenous ethylene glycol.

Methods: Two previously healthy monozygotic adult twin sisters presented with recurrent episodes of apparent ethylene glycol poisoning beginning at age 35, requiring chronic hemodialysis to remove ethylene glycol and its metabolites as well as to restore metabolic homeostasis. The sisters denied ingestion or exposure to ethylene glycol. At their request, they were admitted to hospital under strict supervision to exclude surreptitious ingestion of ethylene glycol and to evaluate the need for treatment. Hemodialysis was withheld during this prospective study. Twin A was admitted for 14 days and twin B for 11 days. Serial biochemical analyses were performed in blood and urine. Clinical exome sequencing and mitochondrial deoxyribonucleic acid sequencing were also completed.

Results: In both twins, ethylene glycol was detected in urine, along with intermittent increases in concentrations of lactate, glycolate, and glycine in blood and/or urine. Blood ethylene glycol concentrations, however, remained <62 mg/L (<1 mmol/L) but became positive soon after discharge. The oxalate concentration remained normal in blood and urine. Plasma and urine amino acid profiles showed intermittent small increases in glycine, serine, taurine, proline, and/or alanine concentrations. Exome sequencing and mitochondrial deoxyribonucleic acid sequencing were non-diagnostic. Neither twin has been admitted with metabolic acidosis nor ethylene glycol poisoning since chronic hemodialysis was started. Twin A developed a calcium oxalate dihydrate lithiasis.

Discussion: Mitochondrial disease, methylmalonic/propionic/isovaleric aciduria, primary hyperoxaluria, and analyte error were all excluded in these twins, as were obvious common environmental exposures.

Conclusion: Detailed investigations were performed in adult monozygotic twin sisters to ascertain whether they were producing endogenous ethylene glycol. Alternative explanations were excluded to the very best of our efforts and knowledge. Global metabolomics, gut microbiome analyses, and whole genome sequencing are pending.

Introduction: Hydroxychloroquine has cardiac and cerebral sodium channel- and human ether-à-go-go-related gene (HERG) potassium channel-blocking effects. This causes depolarization delays, resulting in cardiovascular toxicity with potentially fatal consequences. Despite several supportive care options, hydroxychloroquine poisoning remains difficult to treat. Its high lipid solubility suggests that lipid emulsion therapy might be beneficial; however, no clear evidence regarding its efficacy is available. The aim of this review is to assess the evidence, the outcomes, and adverse events regarding the use of intravascular lipid emulsion therapy as a treatment for hydroxychloroquine poisoning.

Methods: We conducted a systematic search in PubMed, Embase.com, Cochrane Central Register of Controlled Trials (CENTRAL)/Wiley, Web of Science Core Collection/Clarivate Analytics, and Scopus/Scopus.com from inception until 1 November 2023. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion criteria encompassed original observational or interventional studies, case series and case reports describing patients receiving lipid emulsion therapy for hydroxychloroquine toxicity. We extracted clinical data and performed a quality assessment of the included cases. We present the results as a narrative synthesis.

Results: Of 157 identified articles, 16 case reports met the inclusion criteria, reporting on 18 patients. Lipid emulsion therapy was always associated with additional treatments, and detailed information on the circumstances regarding the administration of intravenous lipid emulsion and its presumed effect was often lacking. Fifteen of 18 patients survived to hospital discharge. Some reports described clear and almost immediate clinical improvement after intravenous lipid emulsion administration. No clear adverse effects were reported.

Discussion: A limitation is the reliance on case reports, which varied in the degree of reported details. The administration of multiple therapeutic drugs in most cases made it difficult to attribute survival primarily to lipid emulsion. Publication bias may favour cases with successful outcomes.

Conclusion: Among published case reports, most patients who received lipid emulsion for treatment of hydroxychloroquine poisoning survived. The risk of bias, the small number of reports, and the lack of systematic reporting of both favourable and adverse effects limit any conclusions about the effectiveness of lipid emulsion for hydroxychloroquine poisoning.