Clinical Toxicology最新文献

Introduction: Alcohol withdrawal is typically managed using benzodiazepines. However, modulation of both γ-aminobutyric acid-A and N-methyl-d-aspartate-receptors through ethanol provision may provide an alternative management strategy. This systematic review critically analyses the evidence surrounding the use of oral or intravenous ethanol for the management of alcohol withdrawal syndrome.

Methods: Systematic searches of ProQuest - American Psychological Association, PsycInfo, MEDLINE and PubMed Central, Web of Science and Embase were performed (Prospero registration number: CRD42023425224). Search criteria were: Population = Patients receiving pharmacological interventions to treat or prevent alcohol withdrawal in a healthcare setting. Intervention = intravenous or enteral ethanol. Comparator = standard care, benzodiazepines, carbamazepine, adjunct medications including sedatives, or no comparator. Outcomes = complication rates, symptom scores, length of stay in healthcare settings. Exclusions were: preclinical studies, participants less than 18 years old, non-peer reviewed literature, poor study design or poor data quality. Study quality was assessed using an adapted National Institute for Health and Care Research quality tool. A narrative data synthesis approach was adopted.

Results: Eight thousand two hundred and four studies were retrieved. Ten were included in the final analysis. Overall study quality was poor. Seven studies reported treatment outcomes that were comparable to a control arm or in which ethanol conferred no detrimental effect. Three studies reported positive outcomes, and one study reported worse outcomes following ethanol administration.

Discussion: The review identified heterogeneity in study design and limited reporting surrounding patient demographics, patient alcohol use history and the practicalities of ethanol administration. As such, implementation of ethanol prescribing for the management of alcohol withdrawal is currently limited due to the quality and translatability of existing data surrounding its use.

Conclusions: Further studies are required with more transparent and complete outcome reporting and practical implementation recommendations in order to facilitate the translation of ethanol prescribing for the management of alcohol withdrawal syndrome.

Introduction: Volatile nitrites, such as amyl nitrite, are used recreationally to enhance sexual experience and provide a feeling of euphoria. They are associated with severe adverse reactions including methaemoglobinaemia and maculopathy. The aim of this study was to explore the epidemiology and clinical effects of volatile nitrite exposures reported to the Victorian Poisons Information Centre in Australia over a 10-year period.

Methods: This was a retrospective, observational study of poison centre call records. Data were extracted for all exposures to volatile nitrites reported from 2013 to 2022.

Results: There were 132 calls about volatile nitrites, representing 122 exposures, with a more than five-fold increase in the annual number of exposures (from five in 2013 to 26 in 2022). Ingestion (49.2%) and inhalation (27.9%) were the most common routes of exposure. Seventy-six (62.3%) patients reported one or more symptoms related to volatile nitrite exposure. The most common symptoms were light-headedness/dizziness (20.5%), oro-mucosal irritation (15.6%), ocular irritation (14.8%), nasal irritation (12.3%), and nausea/vomiting (9.8%). Less common, but potentially serious, adverse effects included methaemoglobinaemia (4.1%), hypoxia (1.6%) and hypotension (0.8%). Symptom severity was usually classified as minor (70/76, 92.1%) at the time of the poisons centre call. Fifty-four (44.3%) patients were either in the hospital when the poisons centre was contacted or were referred to the hospital by the poisons centre.

Discussion: The increase in reported volatile nitrite exposures observed in this study aligns with epidemiological data showing an increase in volatile nitrite usage in Australia. The findings about the nature of exposures and symptoms experienced can be used to inform harm reduction and education efforts for community members and health professionals.

Conclusions: Exposures to volatile nitrites reported to an Australian poisons centre increased between 2013 and 2022. More than 40% of exposures resulted in a hospital presentation. Methaemoglobinaemia was reported in 4.1% of cases.

Introduction: While factors like high serum paracetamol (acetaminophen) concentration and delayed acetylcysteine treatment increase hepatotoxicity risk, existing predictive tools, such as the paracetamol concentration aminotransferase activity multiplication product and the psi (ψ) parameter, lack definitive accuracy. This study evaluated the paracetamol psi parameter multiplication product addition against the psi parameter and the paracetamol concentration aminotransferase activity multiplication product for predicting hepatotoxicity following an acute paracetamol overdose.

Methods: A retrospective analysis of patients with acute paracetamol overdose from January 2007 to December 2016 was conducted. The paracetamol psi parameter multiplication product addition, calculated by summing the psi parameter (mmol/L × h) and the paracetamol concentration aminotransferase activity multiplication product (g U/L²), was used. Hepatotoxicity was defined as aspartate or alanine aminotransferase activities ≥1,000 U/L. Diagnostic accuracy was assessed through sensitivity, specificity, the area under the receiver operating characteristic curve, and their corresponding 95% CI, with the optimal cutoff determined using the maximum Youden index method.

Results: The study comprised 421 patients, mostly female (82.9%) with a median age of 23 years. Hepatotoxicity occurred in 13.5% (57 patients). The paracetamol psi parameter multiplication product addition showed an area under the receiver operating characteristic curve of 0.989 (95% CI: 0.974-0.997), with an optimal cutoff at 9.723, providing 96.5% sensitivity and 97.3% specificity. The paracetamol psi parameter multiplication product addition demonstrated superior performance in area under the receiver operating characteristic curve compared to the individual assessments of the psi parameter (0.916; 95% CI: 0.885-0.941) and the paracetamol concentration aminotransferase activity multiplication product (0.901; 95% CI: 0.868-0.928).

Discussion: The paracetamol psi parameter multiplication product addition appears to be a more effective diagnostic tool than the psi parameter or the paracetamol concentration aminotransferase activity multiplication product alone.

Conclusion: Incorporating the paracetamol psi parameter multiplication product addition into clinical protocols could improve paracetamol overdose management by enabling precise identification of individuals at heightened risk for hepatotoxicity, thereby facilitating the customization of treatment approaches.

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: The alpine pit viper, Trimeresurus gracilis, is an endemic species in Taiwan. The incidence of human envenoming is rare.

Case summaries: We present three events in two patients bitten by Trimeresurus gracilis. In the first patient, envenoming inflicted pain, local bleeding, hemorrhagic bulla, and progressive swelling, leading to necrosis of the bite wound. In the second patient, the two snakebites caused pain and progressive swelling. There were no systemic effects such as organ damage or neurological deficits observed. A paraspecific antivenom against Trimeresurus stejnegeri and Protobothrops mucrosquamatus was used to treat both patients, with a favorable outcome in each.

Discussion: Combined with the clinical manifestations of two previously reported cases of Trimeresurus gracilis envenoming, the known effects of Trimeresurus gracilis venom in humans include local toxicities, severe soft-tissue damage, compartment syndrome, and coagulopathy without spontaneous systemic bleeding. The paraspecific antivenom, which has demonstrable cross-neutralization effects in animal studies, appeared to be effective against the local toxicities as the patients showed prompt cessation of the progression of their swelling.

Conclusions: The knowledge of clinical manifestations and management approaches to Trimeresurus gracilis envenoming is helpful for patient care. The use of the paraspecific antivenom should be considered in managing such envenoming.

Introduction: Carbon monoxide poisoning may result in various neurological injuries, including acute symptomatic seizures. We aimed to investigate the long-term risk of epilepsy and status epilepticus in patients with previous carbon monoxide poisoning.

Methods: The study population was derived from the National Health Insurance Service database of the Republic of Korea between 1 January 2002 and 31 December 2021. We included adults with at least one documented visit to medical facilities because of carbon monoxide poisoning (International Classification of Diseases, Tenth Revision, code T58). Patients were matched, on the same index date, with controls, without a T58 code, for age, sex, insurance type, income level, and residence location in a 1:1 ratio. Follow-up continued until death, migration, or the end of the observation period (31 December 2021). The primary outcome was the incidence of epilepsy (codes G40 or R56) and status epilepticus (code G41).

Results: This study included 53,380 patients with carbon monoxide poisoning and 53,380 controls, with 44.2% women and a mean age of 45.7 years. The mean (±SD) follow-up period was 5.7 ± 4.3 years in the carbon monoxide poisoned group and 6.4 ± 4.4 years in controls. The overall risk of epilepsy (adjusted hazard ratio 2.60; 95% CI: 2.43-2.78; P < 0.001) and status epilepticus (adjusted hazard ratio 4.10; 95% CI: 2.84-5.92; P < 0.001) was significantly increased in the carbon monoxide poisoned group compared to controls. The risk of epilepsy and status epilepticus was increased in patients with previous carbon monoxide poisoning, regardless of sex, age or a history of stroke, neurodegenerative diseases, or central nervous system tumour or infection. However, in the subgroup analysis according to age, the highest risk of epilepsy and status epilepticus was observed in patients less than 40 years of age.

Discussion: In this population-based cohort study, previous carbon monoxide poisoning was associated with an increased risk of epilepsy and status epilepticus. The risk was more noticeable in patients aged less than 40 years. Further studies are needed to confirm such an association in other populations.

Conclusions: Previous carbon monoxide poisoning was associated with an increased risk of epilepsy and status epilepticus, particularly in the younger population. The long-term management of survivors of carbon monoxide poisoning should include monitoring for epilepsy and status epilepticus.

Introduction: In 2015, Australia and New Zealand treatment guidelines recommended a 2 h paracetamol serum concentration for risk assessment of unintentional paracetamol liquid exposures. We assess our experience with this approach.

Methods: Retrospective case review of children <6 years-old with liquid paracetamol overdoses referred to a regional poisons information centre January 2017 to August 2022. We extracted data on the exposure and management from the poisons information centre and hospital medical records. We identified additional cases with two paracetamol concentrations obtained from September 2022 to June 2024.

Results: Of 437 paediatric poisonings, 271 were eligible for inclusion. The median age was 24 months, the median time to presentation was 120 min, and paracetamol was the sole ingestant in 92% of cases. Blood testing was recommended in 131 patients (48.3%), occurring at 2 h post-ingestion in 62 patients (47.3%). Testing at a later time was mostly due to delayed presentation, including to hospitals unable to measure paracetamol concentrations. Eighteen patients (16.7%) had repeat blood testing, and five additional cases were identified in the subsequent period. Overall, the concentration decreased in 19 patients (83%), but in three patients it increased, from 73 mg/L to 81 mg/L (0.49-0.54 mmol/L), from 154 mg/L to 179 mg/L (1.03-1.19 mmol/L), and from 56 mg/L to 115 mg/L (0.37-0.77 mmol/L. Symptomatic patients were more likely to receive a second blood test or acetylcysteine while awaiting investigations. Of 19 patients administered acetylcysteine, it was discontinued in five due to low paracetamol serum concentrations. All patients recovered.

Discussion: Guidelines were followed in >90% of patients and this testing regimen shortened length of stay. Based on these data, Australian treatment guidelines now recommend repeat testing for 2 h paracetamol serum concentrations >100 mg/L (0.67 mmol/L).

Conclusion: A paracetamol serum concentration between 2 h and 4 h post-ingestion in children <6 years-old with unintentional poisonings of paracetamol liquid can facilitate medical discharge.