Clinical Toxicology最新文献

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.

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.

Introduction: Rattlesnake (Crotalus spp., Sistrurus spp.) bites in the southwestern United States are associated with significant morbidity. This study aims to describe 25 years of rattlesnake encounters reported to the Arizona Poison and Drug Information Center to identify vulnerable populations and circumstances where encounters occur to create public education to reduce future bites.

Methods: Cases of suspected rattlesnake encounters in Arizona reported to the Arizona Poison and Drug Information Center between 1999 and 2023 were analyzed to identify populations and circumstances associated with encounters.

Results: A total of 3,808 cases were analyzed overall and by age subgroups. Most encounters occurred in men (69.9%), during the evening (16:00-21:59; 49.2%), in summer (41.9%), and close to home (38.2%). Most bites occurred to the lower extremity (51%). Children 0 to 12-years-old have more encounters than those 13-years-old and older in rural zip codes (27.7% versus 14.8%; P = 0.005), during spring (31.8% versus 22.3%; P = 0.0005), and during the evening (64.4% versus 48.1%; P < 0.001).

Discussion: Rattlesnakes are encountered when rattlesnake and human behavior patterns overlap. Many people spend time outside during evening hours in the summer, and valuable resources like food, water, and shelter can be found near houses where humans spend much of their time. Most age groups have similar encounter circumstances but encounters among children 0 to 12-years-old differ in time of day, season, and urbanization level than encounters of those 13-years-old and older. Limitations of this study include underreporting of encounters, incomplete case details, potential reporting bias, potential snake misidentification, and geographic coverage of the poison center.

Conclusion: Prevention of rattlesnake bites by reducing encounters is the most effective way to reduce suffering and healthcare costs. Future steps include creating and disseminating targeted public health education using the data collected.

Introduction: Protonitazene is an opioid belonging to the 2-benzylbenzimidazole structural class. We describe two cases of opioid toxicity involving the reported inhalation of a delta-9-tetrahydrocannabinol vape product in which protonitazene was detected.

Case reports: Case 1 was a young male found unconscious after the reported use of a delta-9-tetrahydrocannabinol vape. He suffered two subsequent apnoeic episodes requiring bag-valve-mask ventilation before eventual recovery. Only protonitazene was detected in blood at a concentration of 0.74 µg/L. Case 2 was a young male who died shortly after being found unresponsive. The postmortem femoral blood concentrations of protonitazene and delta-9-tetrahydrocannabinol were 0.33 µg/L and 2 µg/L, respectively. Analysis of a pod vaping device found in the decedent's hand and a separate e-liquid bottle labelled as delta-9-tetrahydrocannabinol showed a mixture of protonitazene and delta-9-tetrahydrocannabinol.

Discussion: The opioid effects of protonitazene are mediated through β-arrestin2 and mu opioid receptor signalling pathways. Benzimidazole opioids are lipophilic and, when mixed with a suitable solvent, can be used in a vape device. It is anticipated that naloxone would have provided effective reversal of toxicity in our cases.

Conclusions: Novel routes of opioid administration, like vaping, may appear relatively innocuous in comparison to intravenous administration, but opioids may still be absorbed at high concentrations, resulting in severe opioid toxicity or death.

Background: Ethylene glycol poisoning causes metabolic acidosis, organ injury, and death. Ethylene glycol testing is unavailable in many areas. Our laboratory uses an automated glycerol dehydrogenase enzymatic assay to screen for ethylene glycol. We sought to determine how often ethylene glycol results were available within 12 h of the first dose of fomepizole.

Methods: Records from a single poison center were reviewed from December 2016 to December 2019. Cases were identified by searching for cases that received fomepizole. Outcomes included whether results were available within 12 h, and the turnaround time from time of laboratory order to result.

Results: Of the 125 cases of suspected toxic alcohol poisoning identified, 73 had screening for ethylene glycol by enzymatic assay. Results were available within 12 h of the initial fomepizole dose in 58 (79%) cases with a median turnaround time of 391 min.

Discussion: We have demonstrated clinically acceptable turnaround times using an automated screening ethylene glycol assay. The major limitations include lack of approval for this test at this time, the use of voluntarily reported poison center data, and lack of assessment of patient outcomes.

Conclusion: Enzymatic screening for ethylene glycol yielded results within 12 h in 79% of cases.

Introduction: Acute hepatic failure due to yellow phosphorus rodenticide ingestion is often lethal. This study aimed to analyze demographic characteristics and prognostic indicators, focusing on hyperlactataemia as a potential early indicator of mortality in patients poisoned with yellow phosphorus rodenticide.

Materials and methods: This was a retrospective study of 96 patients poisoned with a yellow phosphorus-containing rodenticide (Ratol paste, which contains 3% yellow phosphorus). We examined demographic details, clinical symptoms, and biochemical markers to identify prognostic indicators.

Results: Demographics were similar among survivors and non-survivors. Mortality (36.5%) correlated with a higher ingested dose and treatment delays, with a mean (±SD) of 5.26 ± 2.2 survival days among those who died. Symptoms, including gastrointestinal and neurological features, typically appeared 48 h after ingestion. Non-survivors developed increased aminotransferase activities (74.3%), prolonged prothrombin time (65.7%), and hyperbilirubinaemia (65.7%) during hospitalization, significantly more commonly compared to survivors (P < 0.0001). Hyperlactataemia (lactate concentration >2 mmol/L) was present in 97.1% of non-survivors, with increased serial lactate concentrations observed in 88.6%. The median (interquartile range) admission lactate concentration among non-survivors was 4.6 mmol/L (3.36-7.53 mmol/L), and their peak median (interquartile range) lactate concentration was 6.1 mmol/L (8.74-10.6 mmol/L). In non-survivors, an increased lactate concentration preceded increased aminotransferase activities and prolonged prothrombin time. Logistic regression and receiver operating characteristic curve analysis confirmed that a 24 h lactate concentration ≥2.67 mmol/L predicted death with 94.3% sensitivity and 91.8% specificity.

Discussion: The majority of patients who ingest yellow phosphorus remain asymptomatic initially and typically present to hospital following the onset of gastrointestinal symptoms, usually a day later. As progression to death occurs within a week of yellow phosphorus ingestion in most cases, determining prognosis as early as possible enables swift referral to a liver transplant centre. Based on our study, a 24 h lactate concentration ≥2.67 mmol/L appears to be an early prognostic indicator of death. In another study, a lactate concentration >5.8 mmol/L was found to be a poor prognostic indicator.

Conclusions: Hyperlactataemia on admission and increased serial lactate concentrations appear to be early poor prognostic signs in patients with yellow phosphorus-induced liver failure.

Background: Prompt acetylcysteine treatment with standard doses (300 mg/kg over 21 h in divided doses) is almost universally effective in preventing hepatotoxicity after paracetamol (acetaminophen) overdose. However, hepatotoxicity is reported despite early treatment when paracetamol concentrations exceed 300 mg/L (1,985 μmol/L) at 4 h. Prior studies evaluating high-dose acetylcysteine to treat high-risk ingestions have shown mixed results. We compared outcomes in patients with high-risk ingestions receiving standard or high-dose acetylcysteine.

Methods: Records from a single poison center were reviewed from 1 January 2017 to 31 December 2022. We included cases of acute paracetamol ingestion treated with intravenous acetylcysteine with an initial paracetamol concentration above the "300 mg/L" (1,985 μmol/L) line on the Rumack-Matthew nomogram. We compared standard and high-dose acetylcysteine groups by odds ratios and multivariable logistic regression. We defined hepatotoxicity as aminotransferase activity >1,000 U/L.

Results: We included 190 cases. Fifty-six percent received standard-dose acetylcysteine while 44% received high-dose acetylcysteine. Treatment within 8 h yielded no difference in hepatotoxicity between groups (odds ratio 1.67, 95% CI 0.067-42.3). Among patients treated after 8 h, hepatoxicity was more common in the high-dose group (odds ratio 3.39, 95% CI 1.25-9.2) though odds of liver failure were similar (odds ratio 2.78, 95% CI 0.89-8.69). Eighty-eight percent of patients with hepatotoxicity had elevated aminotransferase activity at presentation. No patient died or received a liver transplant.

Discussion: Rates of hepatotoxicity were low in patients treated within 8 h regardless of acetylcysteine dose. Unexpectedly, high-dose acetylcysteine treatment was associated with an increased odds of hepatoxicity in those treated after 8 h, but most had abnormal aminotransferase activities at presentation and there was no difference in rates of liver failure. Limitations include the use of retrospective, voluntarily reported poison center data.

Conclusions: Prompt treatment with acetylcysteine, regardless of dose, prevented hepatotoxicity in high-risk paracetamol ingestion.

Introduction: The objective of this study was to compare limb circumference measurements between a three-dimensional scanner and a measuring tape.

Methods: Patients older than 18 years, who were bitten by a green pit viper and visited the emergency department between 1 October and 20 December, 2019 were included. Two physicians measured the circumference of a bitten limb and a contralateral unaffected limb twice using both a measuring tape and a three-dimensional scanner. Each patient was measured at the first emergency department visit and again at 24 h, 48 h, and 72 h post-snakebite. There were three points of measurement on both limbs.

Results: There were 408 anatomical locations from 17 patients for measurement. The three-dimensional scanner and the measuring tape demonstrated a very high correlation (r-squared >0.940, P value <0.001) in measuring limb circumferences. Bland Altman plots also demonstrated the two methods measured limb circumferences with similar results with mean differences <1 cm. Intraclass correlation coefficient between the two methods was greater than 0.8 in every site for the lower limbs, but for the upper limbs, most sites had a poor agreement (ranges: 0.073-0.633). For limb volume measurement, the three-dimensional scanner provided excellent and moderate inter and intrarater reliabilities for the lower and upper limbs, respectively.

Discussion: The three-dimensional scanner could be reliably used to assess limb circumference with a strong correlation and with a relatively small error compared with the conventional method. Pictures from the scan can also be constructed to calculate limb volume that could have potential for other clinical purposes such as in evaluating antivenom response for limb swelling.

Conclusions: Circumferences from the three-dimensional scanner were comparable to those from the measuring tape, especially for the lower limbs, and the three-dimensional scanner demonstrated an added value for calculating limb volume.

Introduction: Recent decades have witnessed an extraordinary global crisis of drug misuse. Although opioid analgesics receive the most attention, numerous other drugs have increased rates of misuse.

Ketamine and esketamine: Ketamine and esketamine offer a unique natural experiment to explore two medications that are similar pharmacologically but differ in their availability to users and in their regulation by government agencies.

Misuse and abuse of ketamine and esketamine: Multisystem "mosaic" surveillance of many drugs using real-world data has emerged in recent years. Ketamine and esketamine have been monitored concurrently. Ketamine is much more widely available than esketamine and shows clear signs of increasing misuse and abuse. In contrast, esketamine is difficult to detect in postmarket surveillance even though availability is increasing.

Discussion: Ketamine and esketamine offer insights regarding the safety of prescription medications with the potential for misuse. Since the pharmacology of ketamine and esketamine are similar, the regulatory apparatus may be the primary difference that limits misuse. Ketamine has few restrictions and can be prescribed or administered by many healthcare providers, and is available as an illicit drug. In contrast, the product labeling for esketamine has rigorous restrictions on its use. Many important issues remain to be addressed. We need a more rigorous evaluation of the natural experiment of ketamine and esketamine. How does this experience relate to the introduction of new psychedelics?

Conclusions: Ketamine misuse use and misuse are increasing while esketamine use in increasing, but misuse is not increasing. It is reasonable to reevaluate the regulatory controls on ketamine to reduce its misuse and abuse.

Introduction: Intravenous lipid emulsion is used in the rescue treatment of certain poisonings. A complication is interference with laboratory analyses. The aim of this study was to determine the impact of intravenous lipid emulsion on routine laboratory analysis of coagulation parameters ex vivo and determine if any of the analytical techniques remain reliable.

Methods: Samples were obtained from 19 healthy volunteers and divided in triplicate. One sample served as a control, and the other two were diluted to simulate the treatment of an average adult with Intralipid^® 20 per cent Fresenius Kabi 100 mL (dilution-1) or 500 mL (dilution-2). Coagulation tests performed were prothrombin time, activated prothrombin time, D-dimer concentration and fibrinogen. Coagulation testing was performed by three techniques. Test-1 was performed on a Sysmex CN6000 analyzer. Test-2 was performed with a manual mechanical endpoint method using the semi-automated Stago KC4 Delta. Test-3 involved high-speed centrifugation before repeat testing on the Sysmex CN6000 analyzer.

Results: For test-1, only nine (47 per cent) samples in dilution-1 could be analyzed for coagulation tests, and no coagulation tests could be analyzed for dilution-2 because of lipaemia. For test-2 and test-3, all samples could be analyzed, and all results of both testing methods fell within the limits of the laboratory reference range.

Discussion: Difficulties in laboratory analysis of patients having received intravenous lipid emulsion are due to multiple factors. Most automated coagulation analyzers use optical measurements, which can be unreliable in the presence of a high intravenous lipid concentration. By altering the lipaemia in the testing solution using high-speed centrifugation or by using manual mechanical endpoint detection, we were able to obtain reliable results. These findings are limited by the use of an ex vivo method and healthy volunteers.

Conclusions: This ex vivo model confirms that Intralipid^® interferes with routine coagulation studies. It is important that clinicians are aware and inform their laboratories of its administration.