Clinical Toxicology最新文献

Introduction: Kratom is commonly used by consumers, and the elemental impurity exposure that consumers would have at different kratom ingestion doses has been determined.

Methods: This assessment used original data from independent third-party laboratory testing of kratom products to identify the percentage of products that exceeded permissible daily exposure limits for lead (5 µg/day), nickel (200 µg/day), arsenic (15 µg/day), and cadmium (5 µg/day), the interim reference level for lead in adults (12.5 µg/day), and the tolerable upper intake level for manganese (11 mg/day) and nickel (1 mg/day). We assessed all products regardless of type and then evaluated non-extract products, extract products, and a soda preparation separately for elemental impurities.

Results: Three assessments of elemental impurities in kratom products have been published, totaling 68 products. Assessing all products and assuming a 3 g daily dose of kratom, 7.4% would exceed the permissible daily exposure limits for lead, 0% for nickel, 3.1% for arsenic, and 0% for cadmium. At a kratom dose of 25 g daily, 70.6% would exceed the permissible daily exposure limits for lead, 20.6% for nickel, 9.4% for arsenic, and 0% for cadmium. The interim reference level for lead would be exceeded by 1.5% of products at a kratom daily dose of 3 g and 33.8% of products at 25 g. The tolerable upper intake level for manganese would be exceeded by 12.5% of products at a kratom daily dose of 3 g and 41.7% of products at 25 g. Non-extract products generally contain greater concentrations of elemental impurities than extract products or the soda preparation.

Discussion: Apart from their concentrations in a gram of product, assessing the amount of exposure to elemental impurities at different kratom ingestion doses is also important. Elemental impurities exceeding regulatory permissible concentrations for many products, especially with greater daily kratom ingestion doses, may impact human health.

Conclusions: Some kratom products contain excessive concentrations of elemental impurities of toxicological concern, such as lead and arsenic. Non-extract products (powders, capsules, tablets) generally contain greater concentrations of elemental impurities than extract products or the soda preparation. Daily use of these products can result in exposures exceeding regulatory thresholds and adverse health effects.

Introduction: Poisoning is a leading cause of morbidity and mortality that is increasing in many countries. Better data are needed to understand epidemiology and outcomes of poisoning. This work describes a new poisoning data linkage cohort in New South Wales, Australia (population approximately 8 million).

Methods: This is a longitudinal health record linkage, 2011-2020, including data from: ambulance call-outs, emergency department presentations, hospital admissions, death registrations, the poisons centre, and four tertiary toxicology units. Individuals with poisoning, venomous animal/plant exposures, or adverse drug reaction events were included.

Results: There were 845,217 linkable events relating to 400,642 ambulance, 688,484 emergency department, 682,013 admission, 40,456 toxicology, and 11,879 death records. There were 572,841 people with events; the median age at the time of first event was 57 years, and 51.9% were female. Events leading to patient admission were most commonly adverse drug reactions (n = 511,263), intentional poisonings (n = 68,646), unintentional poisonings (n = 54,840) and animal/plant exposures (n = 11,092). Demographics varied by cause: intentional poisoning (median age 33 years, 61.7% female); unintentional poisoning/animals/plants (median age 43 years, 45% female); and adverse drug reactions (median age 70 years, 54% female). Adolescent females had highest rates of intentional poisoning, while unintentional poisoning had a bimodal distribution, highest in children <5 years old and males aged 20 to 50 years. Substance use disorders were documented comorbidities for 44% of intentional poisoning, 29% of unintentional poisoning, and 13% of adverse drug reaction-related admissions; mood disorders were documented for 54%, 17% and 10% of these admissions, respectively.

Discussion: Poisonings and hospitalised adverse drug reactions are common in New South Wales, affecting approximately 8% of the population in 10 years. This linkage improves understanding of poisoning risks and outcomes in Australia.

Conclusions: This novel data linkage provides a unique opportunity to study poisoning across multiple settings for an individual over an extended period.

Introduction: Severe diquat poisoning often leads to acute kidney injury, gastrointestinal injury, paralytic ileus, rhabdomyolysis, respiratory failure, refractory circulatory failure, and brainstem damage.

Case summary: A previously healthy 38-year-old man was admitted to our hospital with anuria, mild abdominal distension, and calf pain after ingesting diquat (200 g/L) 100 mL approximately 13 h before presentation. His blood diquat concentration was 8.14 µg/L on admission. Gastrointestinal catharsis, haemoperfusion, and haemodiafiltration were performed. Subsequently, he developed marked abdominal distention, impaired consciousness, hypotension, and respiratory failure, leading to death.

Images: Computed tomography revealed gas accumulation in the portal venous system and mesenteric vessels. Moreover, gastrointestinal pneumatosis was present. Computed tomography also revealed changes in the lung, brainstem, and calf muscles.

Conclusion: Diquat poisoning can result in acute kidney injury, hepatic injury, gastrointestinal injury, paralytic ileus, rhabdomyolysis, refractory circulatory failure, brainstem damage, and hepatic portal venous gas, all observed in this patient.

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: Hemotoxicity is common following rattlesnake envenomation. Published experiences with equine-derived crotalidae immune F(ab')₂ antivenom have characterized hemotoxicity as delayed, recurrent, or persistent. This study investigated recovery of hypofibrinogenemia following rattlesnake envenomation treated with equine-derived crotalidae immune F(ab')₂ antivenom.

Methods: This is a retrospective analysis of human rattlesnake envenomations reported to the Arizona Poison and Drug Information Center over four years. We included rattlesnake-envenomated patients who developed hypofibrinogenemia (<1,500 mg/L) and were treated with equine-derived crotalidae immune F(ab')₂ antivenom. The primary outcomes were recovery period (h) and recovery rate (mg/L/h) of hypofibrinogenemia following equine-derived crotalidae immune F(ab')₂ antivenom administration. Collected data included demographics, laboratory values, and antivenom administered. Statistics used were percentages, medians, and Kruskall-Wallis test.

Results: There were 527 rattlesnake envenomations treated with antivenom, of which 80 met the inclusion criteria. Patients receiving treatment with F(ab')₂ antivenom and had a median fibrinogen concentration recovery rate of 62.3 mg/L/h (IQR: 42.0-74.3 mg/L/h) and median recovery period of 19.2 h (IQR: 13.8-26.2 h). There were statistically significant differences between categories for time to antivenom for the median recovery period (P = 0.0154).

Discussion: Hypofibrinogenemia is a common laboratory finding following rattlesnake envenomation in Arizona. This study investigated rattlesnake envenomated patients treated with F(ab')₂ antivenom and monitored fibrinogen concentrations as a surrogate marker of venom toxicity. Additionally, time to administration of F(ab')₂ antivenom was a statistical significant marker of the recovery period from hypofibrinogenemia. Limitations of this study included the geographic coverage of the poison center and exclusion of patients with insufficient laboratory monitoring or those who received another antivenom.

Conclusions: Following rattlesnake envenomation in Arizona, recovery from hypofibrinogenemia was able characterized in a rate (mg/L/h) and period (h) with the quantity and time to administration of antivenom. More studies are needed to assess this finding with other antivenoms and its clinical significance.

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: Envenomation after a North American rattlesnake (Crotalus spp. and Sistrusus spp.) bite is associated with substantial morbidity. Arizona reports the highest number of rattlesnake envenomations annually in the United States. We evaluated the performance of poison and drug information centers for snakebite surveillance, compared with the hospital and emergency department discharge database. We used both datasets to improve the characterization of epidemiology, healthcare costs, and clinical effects of snakebite envenomations in Arizona.

Methods: We identified patients with a snakebite during 2017-2021 using Arizona hospital and emergency department discharge data and snakebite consults with two regional Arizona poison centers. Patients were matched using name and birthdate. The performance of poison center data for snakebite surveillance was evaluated using the percentage of snakebite patients in hospital and emergency department discharge data that consulted with poison centers. Patient demographics, healthcare characteristics, clinical effects, and context of snakebite events were described using both datasets.

Results: In total, 1,288 patients with a snakebite were identified using the Arizona hospital and emergency department discharge data, which resulted in 953 (74%) consultations with poison centers. The median age of patients was 48 years (IQR 28-62 years), and they were predominantly male (66%), White (90%), and non-Hispanic (84%). The median billed charges were US$ 84,880 (IQR US$ 13,286-US$ 168,043); the median duration of a healthcare stay was 34 h (IQR 13-48 h), and 29% of patients were transferred between healthcare facilities. Among 953 consulted poison center calls for a snakebite, a median of 14 vials of antivenom was administered per patient; 375 (60%) bites occurred near the home, and 345 (43%) patients were bitten on a lower extremity. One death was identified.

Discussion: Snakebites in Arizona can cause severe morbidity and require extensive healthcare resources for treatment. Poison centers are valuable for monitoring venomous snakebites in Arizona.

Conclusions: Using hospital and emergency department discharge data with poison center records can improve public health surveillance data regarding snakebite epidemiology and human-snake interaction information and be used to tailor interventions to increase awareness of snake encounters and prevent snakebites.