Clinical Toxicology最新文献

Introduction: Glucagon-like peptide-1 agonists have gained attention in recent years due to their efficacy in managing type II diabetes mellitus and their emerging role in weight management. The purpose of this study was to characterize glucagon-like peptide-1 agonist exposures reported to a single United States regional poison center over nine years, including causes of exposure, associated clinical effects, and potential areas for improving patient education and safety.

Methods: This retrospective cohort study analyzed all poison center calls involving glucagon-like peptide-1 agonists submitted to a single United States regional poison center from 14 January 2014 to 1 May 2023. Data were abstracted from the electronic medical record of the poison center, including demographics, call volume, drug involved, type of exposure, frequency of hypoglycemia, and other side effects.

Results: Two hundred and thirty-seven cases involving glucagon-like peptide-1 agonists were reported to the poison center. The annual number of cases increased sharply over this period. Most patients (n = 166, 70.0%) were females. Most calls (n = 164, 69.2%) were due to unintentional therapeutic errors. Semaglutide was the most frequently involved medication (n = 72, 36.0%). Hypoglycemia was identified in eight patients (3.4%). The lowest mean (±SD) blood glucose concentration in these hypoglycemic patients was 49.6 ± 23.7 mg/dL (2.76 ± 1.3 mmol/L).

Discussion: Unintentional therapeutic errors were involved in 164 (69.2%) cases. Despite the generally mild clinical effects observed in this study, the occurrence of hypoglycemia in a subset of patients, often requiring hospitalization, is of concern. With reports of the acquisition of these medications through online platforms and poorly regulated compounding sources, this trend may pose public health risks.

Conclusions: This study demonstrates the increasing incidence of glucagon-like peptide-1 agonist exposures reported to a United States regional poison center, predominantly due to unintentional overdoses, which highlights the need for ongoing patient education.

Introduction: Delayed neurological sequelae is a common complication following carbon monoxide poisoning, which significantly affects the quality of life of patients with the condition. We aimed to develop a machine learning-based prediction model to predict the frequency of delayed neurological sequelae in patients with carbon monoxide poisoning.

Methods: A single-center retrospective analysis was conducted in an emergency department from January 01, 2018, to December 31, 2023. We analyzed data from patients with carbon monoxide poisoning, which were divided into training and test sets. We developed and evaluated sixteen machine learning models, using accuracy, sensitivity, specificity, and other relevant metrics. Threshold adjustments were performed to determine the most accurate model for predicting patients with carbon monoxide poisoning at risk of delayed neurological sequelae.

Results: A total of 360 patients with carbon monoxide poisoning were investigated in the present study, of whom 103 (28.6%) were diagnosed with delayed neurological sequelae, and two (0.6%) died. After threshold adjustment, the synthetic minority oversampling technique-random forest model demonstrated superior performance with an area under the receiver operating characteristic curve of 0.89 and an accuracy of 0.83. The sensitivity and specificity of the model were 0.9 and 0.8, respectively.

Discussion: The study developed a machine learning-based synthetic minority oversampling technique-random forest model to predict delayed neurological sequelae in patients with carbon monoxide poisoning, achieving an area under the receiver operating characteristic curve of 0.89. This technique was used to handle class imbalance, and shapley additive explanations analysis helped explain the model predictions, highlighting important factors such as the Glasgow Coma Scale, hyperbaric oxygen therapy, kidney function, immune response, liver function, and blood clotting.

Conclusions: The machine learning-based synthetic minority oversampling technique-random forest model developed in this study effectively identifies patients with carbon monoxide poisoning at high risk for delayed neurological sequelae.

Background: Overdose is frequently categorized dichotomously: an inadvertent therapeutic or recreational misadventure versus a deliberate overdose for self-injurious or suicidal purposes. Categorizing overdoses based on this dichotomy of intention is fraught with methodological problems and may result in potentially inappropriate and/or divergent care pathways.

Overdose-related intent lies along a continuum: Suicidality can rapidly shift in magnitude and frequency at different points in time. A patient's overdose may reflect varying degrees of desire to die, ambivalence about living, disregard for risk, or pleasure-seeking. Careful assessment of overdose-related cognitions is warranted in all overdose patients.

The clinical interview is key to understanding an overdose: There is an irreducibly subjective character to an overdose such that a collaborative understanding of an overdose episode can only be discovered by spending time in dialogue with the patient. At the same time, the objective risk factors for and circumstances of the overdose need to be integrated with the subjective experience for a comprehensive prevention approach.

There can be several motivations underlying an overdose: Some overdoses might be wholly inadvertent or simply impulsive. However, if there is some degree of intent present, then the patient who overdosed has attempted to communicate something by means of that overdose, and this message might include something other than the desire to die.

Attending to both the subjective and objective perspectives of an overdose can assist in identifying modifiable risk factors: Overdose-related intent and motivation may be targeted with treatment plans to reduce elevated risk states. Some patient-specific overdose risk factors are modifiable, such as managing mental health and other psychosocial issues, reducing access to lethal means, and promoting safe prescribing and medication administration practices. Other risk factors are either unmodifiable (e.g., personal history of overdose) or involve public health systems.

Conclusions: Overdose-whether involving medications, illicit substances, hazardous chemicals, or otherwise-can be conceptualized as a single behavioral episode with variable intentionality, personal motivations, and risk factors. Clinical/medical toxicologists are uniquely positioned to contribute to personalized risk reduction post-overdose.

Introduction: Nitric and hydrofluoric acids are commonly used in the commercial cleaning industry. We are unaware of reports of nitric acid inhalation forming methaemoglobin. Additionally, methaemoglobinaemia and treatment with methylthioninium chloride (methylene blue) may precipitate clinical uncertainty due to similar wavelengths of absorbance in pulse oximetry.

Cases: We report two patients with respiratory distress from symptomatic methaemoglobinaemia following a prolonged, inhaled occupational exposure to nitric acid in the context of industrial cleaning. Their methaemoglobinaemia was successfully treated with methylthioninium chloride, per remote toxicology advice. However transient oxygen desaturation as reported by pulse oximetry resulted in concern from the treating team.

Discussion: The liberation of oxides of nitrogen from nitric acid bypasses the upper airway without irritation and dissolves in the mucoid lower respiratory tract, oxidising haemoglobin to methaemoglobin. Prolonged undetected exposure with filter saturation, and impaired ventilation is the proposed cause of methaemoglobinaemia in the cases presented. Additionally, methylthioninium chloride absorbs light at the 660 nm wavelength interfering with pulse oximeter interpretation, precipitating the appearance of rapid, severe oxygen desaturation.

Conclusion: Lack of upper airway irritation can lead to unrecognised prolonged nitric acid fume exposure causing methaemoglobinaemia. Remote toxicology advice should include pulse oximeter interference expectations in the presence of methaemoglobinaemia and when administering methylthioninium chloride.

Introduction: Quetiapine shares sodium channel-blocking properties with tricyclic antidepressants. We present the electrographic findings in two patients with severe quetiapine poisoning.

Case summaries: Two patients poisoned with quetiapine presented with impaired consciousness, requiring mechanical ventilation and vasopressor support, with one also experiencing status epilepticus. Their peak serum quetiapine concentrations were 4.52 mg/L and 25.6 mg/L.

Images: On admission, electrocardiograms for both patients revealed a tall R wave in lead aVR, deep S wave in lead I, and QRS complex duration of 120 ms. These findings gradually resolved in parallel with the improvement in their symptoms.

Conclusion: Severe quetiapine poisoning may cause electrographic changes. Further studies are needed to determine the utility of these electrocardiogram findings for predicting the severity of quetiapine poisoning.

Introduction: Fentanyl has replaced diacetylmorphine (heroin) as the primary illicit opioid in the United States. Over the last several years, exposures to illicit fentanyl in small children have increased nationally. We hypothesized that the increase in illicit fentanyl in the community, as measured by regional drug seizures, would be associated with the number of pediatric exposures to illicit fentanyl.

Methods: To assess the number of pediatric illicit fentanyl exposures, we searched the regional poison center database for human exposures in children under 6 years old from January 1, 2019-December 31, 2023. We searched for all cases with fentanyl in the substance field and excluded cases that identified prescription fentanyl in the substance code, product code, or had an exposure reason not consistent with illicit fentanyl. We quantified illicit fentanyl drug seizures in our state by using the Drug Enforcement Administration data. We used Poisson regression to assess the association between drug availability in the community (drug seizures) and pediatric fentanyl exposures.

Results: Between 2019 and 2023, there was an increase in both illicit fentanyl drug seizures (from 11.7 kg/year to 177 kg/year) and pediatric fentanyl exposures (from zero to 16), and there was a significant association (incident rate ratio 1.90; 95% CI: 1.50-2.53; P <0.001) between these rates.

Discussion: We report a strong association between drug availability in the community and pediatric exposures, suggesting that drug seizure data may be a valuable tool for poison centers, medical toxicologists, and public health officials.

Conclusions: Our data suggest that monitoring regional drug seizure data may be a tool to determine new trends in pediatric exposure, guide research in the area, and target outreach and education.

Introduction: Many patients acutely self-poisoned with organophosphorus insecticides have co-ingested ethanol. Currently, profenofos 50% emulsifiable concentrate (EC50) is commonly ingested for self-harm in Sri Lanka. Clinical experience suggests that ethanol co-ingestion makes management more difficult. Therefore, we aimed to determine the relationships between plasma ethanol concentration, plasma profenofos concentration and its toxicokinetics, and clinical outcome in acute profenofos self-poisoning.

Methods: Demographic and clinical data, including a history of ethanol ingestion and blood samples, were prospectively collected from all cases of acute poisoning with profenofos EC50 presenting to Teaching Hospital Peradeniya, Sri Lanka, over four years. Plasma samples were analyzed by gas chromatography-mass spectrometry to quantify the ethanol (n = 99) and profenofos (n = 30 [15 with ethanol, 15 without ethanol]) concentrations. The PKSolver program was used to calculate the toxicokinetic parameters.

Results: Of 99 patients (male 78/99) with acute profenofos self-poisoning, 50 reported a history of ethanol co-ingestion. Plasma from 44 of 99 profenofos-poisoned patients had detectable ethanol concentrations. No statistical difference was observed between the mortality in the ethanol group and the no ethanol group (5/44 [11.4%] versus 3/55 [5.5%]; P = 0.461). Similarly, the median half-lives of plasma profenofos absorption in the ethanol and no ethanol groups (0.1 h and 0.1 h, respectively; time 0-24 h) were not statistically different (P = 0.6594). However, the median half-life of plasma profenofos elimination was significantly longer in the ethanol group than the no ethanol group (23.1 h and 9.9 h, respectively; time 0-24 h; P = 0.0002). According to the regression analysis, the half-life of plasma profenofos elimination was longer by 29.4 h in the ethanol group (P = 0.013).

Discussion: No significant differences in outcomes, including death and endotracheal intubation rates, were found between those who did and did not co-ingest ethanol. No differences were found in toxicokinetic variables between the ethanol and no ethanol groups, but the ethanol group had a longer elimination half-life.

Conclusion: The co-ingestion of ethanol leads to a slowing of the elimination kinetics of profenofos. However, the study did not reveal a significant impact of ethanol co-ingestion on clinical outcomes.

Introduction: Sotalol is a beta-adrenoceptor blocking drug with unique physical and pharmacologic properties. Unlike most beta-adrenoceptor blocking drugs, sotalol is amenable to extracorporeal removal and causes QT interval prolongation and ventricular dysrhythmias. These properties have implications for treating sotalol poisoning.

Patients: Patient 1: A man in his seventh decade of life overdosed on sotalol 9 g and presented with bradycardia, hypotension, QT interval >600 ms and transient ventricular tachycardia. Dopamine, isoprenaline (isoproterenol), and a transvenous pacemaker were used instead of high-dose insulin due to the risk of iatrogenic hypokalemia. Hemodynamics improved, and the pacemaker was removed six days later. Patient 2: A woman in her seventh decade of life on sotalol presented with hypotension in the setting of anuric acute kidney failure. Hypotension worsened after administration of additional sotalol. Hemodialysis was performed for refractory hypotension, followed by improvement in hemodynamics and kidney function.

Discussion: High-dose insulin, a standard therapy in beta-adrenoceptor blocking drug poisoning, causes hypokalemia, which may exacerbate QT interval prolongation and ventricular dysrhythmias in patients with sotalol poisoning. Sotalol is cleared renally and is amenable to extracorporeal removal; hemodialysis may be a useful therapy in patients with cardiotoxicity and concomitant kidney injury.

Conclusions: Chronotropes and overdrive pacing may be preferred therapies for patients with severe sotalol poisoning. If concomitant kidney injury occurs, hemodialysis may be a useful adjunctive therapy.

Introduction: Ibogaine is a psychoactive alkaloid derived from the root bark of the West African shrub Tabernanthe iboga. It is not licensed in the United Kingdom but is used by individuals to alleviate drug or alcohol use.

Methods: A retrospective analysis of telephone enquiries involving ibogaine between 1 January 2012 and 31 December 2022 to the United Kingdom National Poisons Information Service was performed.

Case series: Eleven enquiries relating to seven patients were made to the United Kingdom National Poisons Information Service in this period. Five of these patients were male (71%) with the majority in the age category 31-40 years (57%). All patients presented symptomatically. The circumstances for all seven cases were recorded as "recreational abuse." The exact indication was not specified in three cases but in two cases it was being used to alleviate diacetylmorphine (heroin) use and in another two cases it was being used for relief from insomnia. Three sources of ibogaine were reported - in one case it was bought online, in one case by a dealer and in two cases it was bought from a shaman. When reported, the dose ingested ranged from 5g to 34g. Two patients took it in tablet form and four patients ingested the root bark. The time since exposure, when reported, ranged from 16 h to 1 month. Seven patients experienced neurological symptoms and six displayed features of cardiotoxicity. The most frequently reported features included cardiac arrest, hypoxia, torsade de pointes, QT interval prolongation, coma, convulsions, stupor, bradycardia, vomiting and anxiety.

Conclusions: Individuals using ibogaine in variable doses to self-treat for drug use are at risk of developing severe cardiotoxicity and neurological symptoms. Further studies to quantify dose-response relationship and to further improve knowledge of its pharmacokinetics are required.