Clinical Toxicology最新文献

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.

Introduction: Methylthioninium chloride is used for multiple treatment purposes and is sometimes administered through peripheral intravenous lines. We highlight the potential adverse effects of methylthioninium chloride extravasation during continuous peripheral intravenous administration.

Case summary: A 38-year-old woman presented to the emergency department with multifactorial hypovolemic and septic shock. She was treated with a continuous peripheral infusion of intravenous methylthioninium chloride for shock refractory to multiple vasopressors.

Images: One day after administration commenced, the patient developed blue staining of the left upper arm due to extravasation of methylthioninium chloride proximal to the site of infusion. Further images show its later spread.

Conclusion: While reported cases of methylthioninium chloride extravasation are rare, it is our preference that methylthioninium chloride should be administered through a central line in cases of continuous infusion due to the risk of potential toxicity from extravasation.

Introduction: The VipGrade^® is a French electronic clinical tool that was created in 2022 to help frontline clinicians grade envenomations due to European Vipera spp. and decide whether to use specific immunotherapy. The aim of this study was to test VipGrade^® on a paediatric retrospective cohort (2001-2022) of cases of Vipera spp. envenomation and evaluate the concordance with the initial grading assigned by clinicians on admission.

Methods: For each child in the cohort (n = 116), VipGrade^® was applied by a single physician unaware of the initial clinical grading. We compared VipGrade^® results with those obtained at the time of admission using the Audebert-Boels classification system.

Results: The proportion of discrepancies represented 26% of initial grade I (n = 39) cases, meaning that 10 children were upgraded to grade IIa (n = 9) or IIb (n = 1). The main reason was the VipGrade^® cut-off for oedema size (4 cm) to distinguish grade I from grade II, while oedema evaluation using the Audebert-Boels clinical classification differs in this regard. The global correlation κ score was equal to 0.78; 0.71 with the exception of grades 0 (which is not usually a diagnostic issue); 0.64 considering both results for young children (age <6 years, n = 51) and 0.79 for older ones.

Discussion: Upgrading cases inappropriately could have a major impact on treatment and the use of the antivenom. Even if specific immunotherapy with Viperfav^® (MicroPharm Ltd, Newcastle Emlyn, Carmarthenshire, SA38 9BY, United Kingdom) is safe, its use when inappropriate cannot be justified, particularly in times of supply shortage, as we have experienced over the last 10 years.

Conclusion: The current version of the VipGrade^® electronic clinical tool produces a different distribution of envenomation grades, notably in grade I by overgrading a substantial number of cases. We suggest creating a paediatric version that incorporates the same oedema evaluation method as the Audebert-Boels clinical classification but also includes a more refined definition of "local or regional" oedema.

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.

Background: In 2020, there were 36.7 million reported falls among older adults (65+) in the United States. Ethanol and other sedating substances may increase fall risk among older adults due to their effect on cognitive and physical function. We estimate the prevalence of these substances in blood specimens of older adults presenting with a fall injury at selected trauma centers.

Methods: The initial study collected blood specimens from May 2020 through July 2021 from adults undergoing a trauma team evaluation at selected United States Level 1 trauma centers. We limited our study to older adults evaluated after a fall (n = 1,365) and selected a random sample (n = 300) based on age, sex, and trauma-center quotas. Medical health records and blood specimens obtained at trauma center presentation were analyzed. We estimated the prevalence of ethanol, benzodiazepines, cannabinoids, and opioids in the blood specimens. Two-sample tests of binomial proportions and Chi-square two-tailed tests were used to compare prevalence estimates of substances by demographic characteristics.

Results: At least one substance was detected among 31.3% of samples analyzed. Prevalences of specific substances detected were 9.3% (95% CI: 6.0-12.6%) for benzodiazepines, 4.3% (95% CI: 2.0-6.7%) for cannabinoids, 8.0% (95% CI: 5.2-11.7%) for ethanol, and 15.0% (95% CI: 10.9-19.1%) for opioids. There were 18 deaths (6%; 95% CI: 3.6-9.3%). One-third of decedents had at least one substance detected in their blood.

Discussion: Opioids were the most frequently detected substance, followed by benzodiazepines, ethanol, and cannabinoids. Substance use prevalence was not uniform across demographics, with differences observed by sex and age.

Conclusions: This study provides insight into the frequency of the presence of substances that may contribute to fall risk and serious injury among older adults. Screening older adults for substances that impair cognitive and physical function can enhance clinical fall prevention efforts.