Clinical Toxicology最新文献

Introduction: Alkyl nitrites ("poppers") are used recreationally for sexual enhancement, muscle relaxation, and euphoria. However, they can be toxic and cause adverse reactions such as methemoglobinemia. While inhalation is the typical route of usage, the New York City Poison Center has noted an increase in calls related to ingestion. Given the uncertainty of usage instructions at the point of sale, our study aimed to assess instructions provided to consumers about alkyl nitrite use and to evaluate the proximity and co-sale of alkyl nitrites with similarly appearing energy drink shots.

Methods: We conducted a cross-sectional convenience sample survey of smoke shops, cannabis dispensaries, and exotic shops within the catchment area of an urban poison center. Plain clothes "investigators" (i.e., the researchers) visited these retailers and followed a predetermined protocol and script to request information regarding the availability and usage of alkyl nitrites. Additionally, the researchers attempted to visually assess the proximity of alkyl nitrites to similarly appearing energy drink shots during their visit.

Results: Ninety-eight stores were visited in the New York City area, and eighty-six met the inclusion criteria of selling alkyl nitrites. After being questioned, forty-one (48%) retailers advised inhalation. Thirty-eight (44%) vendors were unsure how to use alkyl nitrites or refused to answer. Seven (8%) stores recommended ingestion. Furthermore, fifty-one (59%) vendors also sold 5-Hour Energy^® drinks and alkyl nitrites were located near these energy drink shots in twenty (39%) of these fifty-one stores.

Discussion: Many commercial alkyl nitrite retailers in our survey area lack knowledge or provide potentially inaccurate information regarding the use of alkyl nitrites. Additionally, alkyl nitrites are often sold alongside commercial energy drinks, potentially increasing the risk of incidental ingestion.

Conclusions: Further research is necessary to determine the impact of these patterns of sale and potential misinformation. Discussing preliminary results of our survey with the New York City Department of Health led to the rapid creation of an informational poster and local outreach. Clinicians should report cases of alkyl nitrite use to their regional poison center to allow for more targeted and timely public health intervention.

Introduction: Patients poisoned with gamma-hydroxybutyrate may need urgent medical treatment. The clinical manifestations are heterogeneous, and the level of consciousness is often unstable, with fluctuations between agitation and coma. We aimed to investigate the accuracy of the clinical diagnosis of gamma-hydroxybutyrate poisoning compared to laboratory findings in blood samples.

Methods: We did a prospective observational study, including patients ≥16 years of age admitted to hospital with a clinical diagnosis of gamma-hydroxybutyrate poisoning. The diagnosis was established by the doctor treating the patient based on the clinical information and/or information from the patient and/or the patient's companions. Blood samples were taken at admission and analyzed using ultra high-performance liquid chromatography-tandem mass spectrometry.

Results: There were 87 patients with a median age of 35 years (IQR: 30-42 years), and 58.6% (51/87) were male. Gamma-hydroxybutyrate was found in blood samples taken from 60 (69.0%) patients. The median Glasgow Coma Scale of all patients on arrival at hospital was 6 (IQR: 3-10), and 53.3% of the patients who tested positive for gamma-hydroxybutyrate presented with a Glasgow Coma Scale of 3. The Glasgow Coma Scale was significantly lower (P <0.001) among patients who tested positive for gamma-hydroxybutyrate, and was inversely correlated with gamma-hydroxybutyrate concentrations. Among the 60 patients testing positive for gamma-hydroxybutyrate, 28 (46.7%) needed treatment in an intensive care unit, and three (5.0%) required endotracheal intubation. In 58 (96.7%) of the 60 patients who tested positive for gamma-hydroxybutyrate, other drugs were also found, most frequently amfetamines, cocaine, and benzodiazepines.

Discussion: The frequent co-consumption of other psychoactive drugs makes the clinical diagnosis of gamma-hydroxybutyrate challenging, and poisoning with other central nervous system depressants was frequently observed among those patients testing negative for the gamma-hydroxybutyrate.

Conclusions: In only two out of three patients with clinically suspected gamma-hydroxybutyrate poisoning was gamma-hydroxybutyrate found in a blood sample, indicating that clinicians might overdiagnose gamma-hydroxybutyrate poisoning.

Background: Propanil toxicity is characterised by severe prolonged methaemoglobinaemia, cyanosis, acidosis, and progressive end-organ dysfunction. In vitro studies report propanil-induced kidney toxicity, which has not been studied clinically. This study determined the incidence of acute kidney injury and of methaemoglobinaemia after propanil self-poisoning and reported the diagnostic performance of novel and traditional biomarkers of acute kidney injury.

Methods: Sixty-seven previously healthy patients were recruited following acute propanil self-poisoning, between October 2010 and October 2014. Concentrations of serum biomarkers and urine biomarkers normalised for urine creatinine excretion were measured. Plasma and urine concentrations of propanil, its main metabolite 3,4-dichloroaniline, the antidote methylthioninium chloride (methylene blue), and methaemoglobin levels were measured.

Results: Kidney biomarkers were measured in 52 of the 67 patients, with 40% developing acute kidney injury (stage 1 [32%] and stage 2 [8%]). Blood methaemoglobin levels were recorded in 23 patients. Normalised urine biomarker concentrations of kidney injury molecule-1, trefoil factor 3, neutrophil gelatinase-associated lipocalin and beta₂ microglobulin increased in patients who developed acute kidney injury, but only trefoil factor 3 and cystatin C showed a significantly predicted acute kidney injury at 16-24 h and 8-16 h post-ingestion, respectively. In contrast, serum creatinine concentrations had a very good diagnostic performance throughout the 24 h post-ingestion period, with area under the receiver operating characteristic curve values of 0.79-0.96. Blood methaemoglobin levels were higher in patients with acute kidney injury and correlated with plasma propanil and 3,4-dichloroaniline concentrations. Concentrations of serum creatinine, urine beta₂ microglobulin, and trefoil factor 3 significantly correlated with plasma and urine concentrations of propanil, 3,4-dichloroaniline, and methylthioninium chloride.

Discussion: Severe methaemoglobinaemia can impair oxygen delivery and may cause acute ischaemic kidney injury. The poor diagnostic performance of novel biomarkers may be attributed to non-renal factors influencing creatinine concentration or an unusual site or mechanism of nephrotoxicity after propanil poisoning.

Conclusions: Patients with propanil self-poisoning exhibited reversible kidney injury diagnosable using serum creatinine concentrations within 4 h. Although other biomarkers were increased, they were not effective for early diagnosis.

Introduction: Ivabradine was approved for use in the United States in 2015 for the management of heart failure. It acts through inhibition of sodium channels found in cardiac myocytes (the "funny" pacemaker current, I_f), which reduces heart rate without significantly affecting inotropy.

Methods: We queried the National Poison Data System^® for reported ivabradine exposures from April 15, 2015-December 31, 2023. Age was stratified into child (0-5 years), adolescent (6-17 years), adult (18-64 years) and geriatric (65+ years). Other descriptive statistics gathered included patient sex, management site, and medical outcome as coded by America's Poison Centers^®.

Results: There were 240 ivabradine exposures, with 55.0% managed on-site and not transferred to a healthcare facility. The most common reported symptom was bradycardia, reported in 36 patients (15.1%). There were 139 cases that were followed to a known outcome. Within this cohort, 60%, 14%, and 27% of patients suffered no effect, minor effect, or moderate effect, respectively. Exposures in children comprised 18.8% of cases; none required intervention. Intentional self-harm exposures comprised 17.1% of all cases and were more likely to have worse outcomes. Five adult patients received intensive therapy (endotracheal intubation, vasopressors, cardiac pacing, hemodialysis). There were no reported deaths from ivabradine exposure.

Discussion: This study has limitations. First, our data source was limited by being retrospective and incomplete; we could only study the information that was reported to poison centers, and exposures were not confirmed by laboratory testing. It is possible that cases without further follow-up had other treatments and clinical effects not reported here. Finally, reports to poison centers likely underestimate the true number of ivabradine exposures.

Conclusion: Adults with unintentional, asymptomatic exposures to ivabradine may be candidates for home monitoring. In ivabradine exposures refractory to medical management, clinicians should consider cardiac pacing or other supportive measures as a temporizing measure.

Introduction: Despite the widely accepted use of methylthioninium chloride (methylene blue) to treat methemoglobinemia, data regarding clinical outcomes are sparse. We sought to better elucidate the efficacy and tolerability of methylthioninium chloride.

Methods: We identified all cases reported to the New York City Poison Center from 2000 to 2024 in which methylthioninium chloride was administered for methemoglobinemia. We extracted clinical data from these cases, which we assessed using primarily descriptive statistics.

Results: A total of 185 cases were included. The median methemoglobin level was 29% (IQR: 19-42%). Implicated xenobiotics were most frequently volatile nitrites (41%), local anesthetics (15%), and dapsone (11%). The median methylthioninium chloride dose was 1 mg/kg (IQR: 1-2 mg/kg; range: 0.5-4 mg/kg). Multiple doses of methylthioninium chloride were administered in 11% of cases, with a median total dose of 2 mg/kg (IQR: 2-3 mg/kg), the majority of which were associated with volatile nitrites (n = 7) or dapsone (n = 6). Improvement after administration of methylthioninium chloride was reported in 98% of cases (95% CI: 96-100%). Adverse effects attributable to methylthioninium chloride were reported in nine cases (4.9%; 95% CI: 4.6-5.1%), including one instance of hemolysis. Glucose-6-phosphate dehydrogenase activity was found to be deficient in two of seven patients tested, only one of whom did not improve after methylthioninium chloride. Two deaths occurred in this series, both associated with sodium nitrite exposure.

Discussion: Most patients with methemoglobinemia improved after 1-2 mg/kg of methylthioninium chloride, supporting current treatment recommendations. Despite few instances of glucose-6-phosphate dehydrogenase activity testing, major adverse effects attributable to methylthioninium chloride were extremely rare. A relatively large proportion of cases receiving multiple doses were associated with dapsone exposure.

Conclusions: In this series, methylthioninium chloride was both efficacious and well tolerated in patients with methemoglobinemia, with a single dose of 1-2 mg/kg being sufficient to treat most patients.

Introduction: Chronic loperamide overdose is associated with cardiotoxicity. We describe the toxicokinetics of loperamide and N-desmethyl loperamide, and their concentration-response relationship on cardiotoxicity in newly described and published cases.

Materials and methods: We obtained serial loperamide and N-desmethyl loperamide concentrations, and corresponding electrocardiographic intervals in three episodes (two patients) of loperamide-related cardiotoxicity. A toxicokinetic and toxicodynamic analysis was undertaken that included data from previous publications to explore the relationship between these variables.

Results: Patients presented with dizziness, bradycardia, loss of consciousness, and jerking or ventricular tachycardia after taking loperamide 320-400 mg/day for weeks or years. In one patient, ventricular tachycardia occurred on days two and three post-admission. Prolonged electrocardiographic intervals resolved after approximately five days. Admission loperamide concentrations were 5.37-288 μg/L and the terminal elimination half-lives were 21.3-38.7 h. Admission N-desmethyl loperamide concentrations were 87.67-256.34 μg/L and the terminal elimination half-life was 31.9-88.9 h. Overall, there were 42 loperamide and 35 N-desmethyl loperamide concentrations with paired electrocardiographic data, and the concentration-response relationship was derived using a maximum effect (Emax) model. Lower loperamide concentrations were associated with electrocardiographic abnormalities, compared to N-desmethyl loperamide concentrations. The total relative loperamide concentration, which combines both concentrations into a single value using in vitro inhibitory potencies at cardiac ion channels, out-performed either parent or metabolite concentrations alone for predicting cardiotoxicity on receiver operating characteristic curves.

Discussion: Loperamide and N-desmethyl loperamide have long elimination half-lives causing prolonged cardiotoxicity. Higher loperamide and N-desmethyl loperamide concentrations are associated with prolonged electrocardiographic intervals.

Conclusions: Patients with chronic loperamide overdose are at risk of cardiotoxicity that persists for days due to persistent loperamide and N-desmethyl loperamide concentrations. We believe patients with loperamide overdose need an admission electrocardiograph and continuous monitoring until electrocardiographic changes resolve.