Acute arsenic exposure secondary to deliberate self-poisoning with sheep dip.

A 53-year-old male patient presented to a regional hospital Emergency Department approximately 2 h post an intentional ingestion of Coopers Instant Wetting Powder Sheep Dip (66% arsenic trioxide, 23% sulphur and 0.42% rotenone), mixed in 600 mL water, as a suicide attempt. On arrival to the Emergency Department, the patient had nausea, vomiting and diarrhoea. Seven hours post ingestion, hypotension developed (BP 90/60 mmHg) and intravenous fluids were commenced. He later developed QTc prolongation. He was treated with 2,3-Dimercapto-1-propanesulfonic acid (DMPS) and N-acetylcysteine and improved without development of neurology. Further investigation of NAC efficacy in humans in the setting of acute arsenic poisoning is required and the optimal duration of treatment and dosing needs to be established. This case highlights an uncommon poisoning which presented to the Emergency Department, the acute symptoms of arsenic toxicity and considerations for management.

Co-exposure to gamma-hydroxybutyrate is associated with attenuated neuropsychiatric and stimulant effects of metamfetamine.

INTRODUCTION: Acute metamfetamine toxicity is characterized by stimulant effects and neuropsychiatric disturbance, which is attenuated by gamma-aminobutyric acid type A receptor agonists including benzodiazepines. We utilized clinical registry data to examine the effect of co-exposure to a gamma-aminobutyric acid type B receptor agonist (gamma-hydroxybutyrate) in illicit drug cases with analytically confirmed exposure to metamfetamine. METHODS: The Emerging Drugs Network of Australia Victoria is an ethics board-approved prospective registry collecting clinical and analytical data (utilising blood samples) on emergency department illicit drug presentations. Comparison groups were defined by analytically confirmed exposure: lone metamfetamine, metamfetamine plus gamma-hydroxybutyrate, metamfetamine plus benzodiazepine, metamfetamine plus gamma-hydroxybutyrate plus benzodiazepine. Cases with co-exposure to other stimulants or sedatives were excluded. RESULTS: Median metamfetamine blood concentrations were significantly greater in metamfetamine plus gamma-hydroxybutyrate (n = 153, median = 0.20 mg/L, interquartile range: 0.10-0.32 mg/L, 95 per cent confidence interval: 0.20-0.23 mg/L) and metamfetamine plus gamma-hydroxybutyrate plus benzodiazepine (n = 160, median = 0.20 mg/L, interquartile range: 0.10-0.30 mg/L, 95 per cent confidence interval: 0.20-0.30 mg/L) positive groups compared to gamma-hydroxybutyrate negative groups including metamfetamine (n = 81, median = 0.10 mg/L, interquartile range: 0.05-0.21 mg/L, 95 per cent confidence interval: 0.09-0.18 mg/L) and metamfetamine plus benzodiazepine (n = 73, median = 0.10 mg/L, interquartile range: 0.06-0.20 mg/L, 95 per cent confidence interval: 0.09-0.20 mg/L) groups (P < 0.0004). Presenting heart rate in metamfetamine plus gamma-hydroxybutyrate cases (n = 153, median = 72 beats per minute, interquartile range: 63-86 beats per minute, 95 per cent confidence interval: 70-78 beats per minute) was significantly lower than metamfetamine plus benzodiazepine cases (n = 73, median = 84 beats per minute, interquartile range: 73-98 beats per minute, 95 per cent confidence interval: 80-90 beats per minute, P < 0.0001), and lone metamfetamine cases (n = 81, median = 110 beats per minute, interquartile range: 87-131 beats per minute, 95 per cent confidence interval: 93-120 beats per minute, P < 0.0001). Presenting temperature in metamfetamine plus gamma-hydroxybutyrate cases (median = 35.8 °C, interquartile range: 35.0-36.2 °C, 95 per cent confidence interval 35.6-35.9 °C) was significantly lower than metamfetamine plus benzodiazepine cases (median 36.2 °C, interquartile range 35.7-36.6 °C, 95 per cent confidence interval, 36.0-36.4 °C, P = 0.017), and lone metamfetamine cases (median = 36.5 °C, interquartile range: 35.8-37.1 °C, 95 per cent confidence interval: 36.2-36.7 °C, P < 0.0001). Median presenting systolic blood pressure was significantly (P ≤ 0.001) lower in benzodiazepine positive groups (metamfetamine plus benzodiazepine median = 120 mmHg, interquartile range: 109-132 mmHg, 95 per cent confidence interval: 116-124 mmHg and metamfetamine plus benzodiazepine plus gamma-hydroxybutyrate median = 124 mmHg, interquartile range: 110-137 mmHg, 95 per cent confidence interval: 120-129 mmHg). Incidence of sedation (Glasgow Coma Scale less than 9) was significantly greater in metamfetamine plus gamma-hydroxybutyrate cases (63 per cent) compared to metamfetamine plus benzodiazepine cases (27 per cent, P < 0.0001) and lone metamfetamine cases (15 per cent, P < 0.0001). Incidence of agitation was significantly lower in metamfetamine plus gamma-hydroxybutyrate plus benzodiazepine cases (17 per cent, P < 0.0001) and metamfetamine plus gamma-hydroxybutyrate cases (34 per cent, P = 0.0004) compared to lone metamfetamine cases (58 per cent). DISCUSSION: Differences in gamma-aminobutyric acid type A and B receptor physiology may offer a gamma-aminobutyric acid type B agonist-facilitated alternative pharmacodynamic mechanism able to attenuate metamfetamine stimulant and neuropsychiatric toxicity. CONCLUSION: Metamfetamine intoxicated patients with analytically confirmed co-exposure to gamma-hydroxybutyrate had significantly reduced heart rate, body temperature and incidence of agitation compared to patients with lone metamfetamine exposure. Metamfetamine intoxicated patients with analytically confirmed co-exposure to a benzodiazepine had significantly reduced systolic blood pressure compared to patients with lone metamfetamine exposure. We hypothesize that gamma-aminobutyric acid type B receptor agonists may be beneficial in the management of acute metamfetamine toxicity.

From signal to alert: A cluster of exposures to counterfeit alprazolam tablets containing five novel benzodiazepines.

OBJECTIVE: To illustrate the toxicosurveillance role of the Emerging Drugs Network of Australia - Victoria (EDNAV) project in informing timely harm minimisation interventions. METHODS: Utilisation of an ethics approved clinical registry storing de-identified clinical and analytical data on Victorian ED illicit drug-related presentations. RESULTS: In April 2022, six adults presented to hospital with varying levels of sedation, following the use of counterfeit benzodiazepines. Comprehensive toxicological analysis identified five separate novel benzodiazepines within blood samples from each patient. A public 'Drug Alert' was subsequently issued, and local emergency physicians were notified. CONCLUSION: Toxicosurveillance projects, such as EDNAV, are critical to the continued monitoring and reporting of illicit substance use in the community.

Non-fatal intoxications involving the novel benzodiazepine clonazolam: case series from the Emerging Drugs Network of Australia - Victoria project.

INTRODUCTION: Clonazolam is an unregistered novel benzodiazepine which emerged in global illicit drug markets in 2014. We describe the clinical features of four cases of non-fatal clonazolam mono-intoxications from patients presenting to emergency departments in Australia. CASES: Four patients aged between 16 and 19 years presented to hospital with a sedative toxidrome (Glasgow Coma Scale range 8-13) and elevated heart rate (median heart rate 100 beats per minute, range 92-105) following reported benzodiazepine exposure. Three patients reported the use of a large quantity (7-20 tablets) of Xanax®, a brand of alprazolam not commercially available in Australia. Two patients required nasopharyngeal airway insertion following the development of airway obstruction. The median time to return of a normal conscious state (Glasgow Coma Scale 15) was 23 h (range 5-30 h). Clonazolam (range 0.2-2.1 µg/L) and its main metabolite 8-aminoclonazolam (range 5.9-19.1 µg/L) were the only substances detected by liquid chromatography-tandem mass spectrometry in blood samples of all patients. CONCLUSION: Clonazolam intoxication resulted in sedation with mild sinus tachycardia. Three patients who reported multiple tablet exposures experienced prolonged sedation, and two of these patients developed airway obstruction. In this series, clonazolam was unknowingly ingested through possible illicit substitution within an unregulated counterfeit benzodiazepine product.

A risk-based approach to community illicit drug toxicosurveillance: operationalisation of the Emerging Drugs Network of Australia - Victoria (EDNAV) project.

INTRODUCTION: The Emerging Drugs Network of Australia - Victoria (EDNAV) project is a newly established toxicosurveillance network that collates clinical and toxicological data from patients presenting to emergency departments with illicit drug related toxicity in a centralised clinical registry. Data are obtained from a network of sixteen public hospital emergency departments across Victoria, Australia (13 metropolitan and three regional). Comprehensive toxicological analysis of a purposive sample of 22 patients is conducted each week, with reporting of results to key alcohol and other drug stakeholders. This paper describes the overarching framework and risk-based approach developed within Victoria to assess drug intelligence from EDNAV toxicosurveillance. METHODS: Risk management principles from other spheres of public health surveillance and healthcare clinical governance have been adapted to the EDNAV framework with the aim of facilitating a consistent and evidence-based approach to assessing weekly drug intelligence. The EDNAV Risk Register was reviewed over the first two years of EDNAV project operation (September 2020 - August 2022), with examples of eight risk assessments detailed to demonstrate the process from signal detection to public health intervention. RESULTS: A total of 1112 patient presentations were documented in the EDNAV Clinical Registry, with 95 signals of concern entered into the EDNAV Risk Register over the two-year study period. The eight examples examined in further detail included suspected drug adulteration (novel opioid adulterated heroin, para-methoxymethamphetamine adulterated 3,4-methylenedioxymethamphetamine (MDMA)), drug substitution (25B-NBOH sold as lysergic acid diethylamide, five benzodiazepine-type new psychoactive substances in a single tablet, protonitazene sold as ketamine), new drug detection (N,N-dimethylpentylone), contamination (unreported acetylfentanyl) and a fatality subsequent to MDMA use. A total of four public Drug Alerts were issued over this period. CONCLUSIONS: Continued toxicosurveillance efforts are paramount to characterising the changing landscape of illicit drug use. This work demonstrates a functional model for risk assessment of illicit drug toxicosurveillance, underpinned by analytical confirmation and evidence-based decision-making.

The Emerging Drugs Network of Australia - Victoria Clinical Registry: A state-wide illicit substance surveillance and alert network.

OBJECTIVES: With an increasingly dynamic global illicit drug market, including the emergence of novel psychoactive substances, many jurisdictions have moved to establish toxicosurveillance systems to enable timely detection of harmful substances in the community. This paper describes the methodology for the Emerging Drugs Network of Australia - Victoria (EDNAV) project, a clinical registry focused on the collection of high-quality clinical and analytical data from ED presentations involving illicit drug intoxications. Drug intelligence collected from the project is utilised by local health authorities with the aim to identify patterns of drug use and emerging drugs of concern. METHODS: The project involves 10 public hospital EDs in Victoria, Australia. Patients 16 years and over, presenting to a network ED with a suspected illicit drug-related toxicity and a requirement for venepuncture are eligible for inclusion in the study under a waiver of consent. Clinical and demographic parameters are documented by site-based clinicians and comprehensive toxicological analysis is conducted on patient blood samples via specialised forensic services. All data are then deidentified and compiled in a project specific database. RESULTS: Cases are discussed in weekly multidisciplinary team meetings, with a view to identify potentially harmful substances circulating in the community. High-risk signals are escalated to key stakeholders to produce timely and proportionate public health alerts with a focus on harm minimisation. CONCLUSIONS: The EDNAV project represents the first centralised system providing near real-time monitoring of community drug use in Victoria and is fundamental in facilitating evidence-based public health intervention.

Characteristics and time course of benzodiazepine-type new psychoactive substance detections in Australia: results from the Emerging Drugs Network of Australia - Victoria project 2020-2022.

INTRODUCTION: The emergence of benzodiazepine-type new psychoactive substances (NPSs) are a growing international public health concern, with increasing detections in drug seizures and clinical and coronial casework. This study describes the patterns and nature of benzodiazepine-type NPS detections extracted from the Emerging Drugs Network of Australia - Victoria (EDNAV) project, to better characterise benzodiazepine-type NPS exposures within an Australian context. METHODS: EDNAV is a state-wide illicit drug toxicosurveillance project collecting data from patients presenting to an emergency department with illicit drug-related toxicity. Patient blood samples were screened for illicit, pharmaceutical and NPSs utilising liquid chromatography-tandem mass spectrometry. Demographic, clinical, and analytical data was extracted from the centralised registry for cases with an analytical confirmation of a benzodiazepine-type NPS(s) between September 2020-August 2022. RESULTS: A benzodiazepine-type NPS was detected in 16.5 % of the EDNAV cohort (n = 183/1112). Benzodiazepine-type NPS positive patients were predominately male (69.4 %, n = 127), with a median age of 24 (range 16-68) years. Twelve different benzodiazepine-type NPSs were detected over the two-year period, most commonly clonazolam (n = 82, 44.8 %), etizolam (n = 62, 33.9 %), clobromazolam (n = 43, 23.5 %), flualprazolam (n = 42, 23.0 %), and phenazepam (n = 31, 16.9 %). Two or more benzodiazepine-type NPSs were detected in 47.0 % of benzodiazepine-type NPS positive patients. No patient referenced the use of a benzodiazepine-type NPS by name or reported the possibility of heterogenous product content. CONCLUSION: Non-prescription benzodiazepine use may be an emerging concern in Australia, particularly amongst young males. The large variety of benzodiazepine-type NPS combinations suggest that consumers may not be aware of product heterogeneity upon purchase or use. Continued monitoring efforts are paramount to inform harm reduction opportunities.

Assessment of the Availability, Cost, and Motivations for Use over Time of the New Psychoactive Substances-Benzodiazepines Diclazepam, Flubromazepam, and Pyrazolam-in the UK.

INTRODUCTION: There has been increasing interest in the availability of non-prescription benzodiazepines and their sale as new psychoactive substances. We wanted to determine UK availability from Internet suppliers and motivations for use of three benzodiazepines (diclazepam, flubromazepam, and pyrazolam). METHODS: In November 2014 and March 2016, using the European Monitoring Centre for Drugs and Drug Addiction Snapshot Methodology, Internet search engines ( google.co.uk , uk. yahoo.com and ask.com.uk ) were searched using the terms 'buy diclazepam', 'buy flubromazepam' and 'buy pyrazolam'. Threads from drug-user forums ( bluelight.org , drugs-forum.com , erowid.org , legalhighsforum.com ) were analysed using a general inductive approach. Data were converted into price per gram/pellet to allow cost comparisons and to determine motivations for use. RESULTS: There was an increase in websites selling these benzodiazepines between 2014 and 2016: diclazepam (49 in 2014 to 55 in 2016), pyrazolam (33 to 35), and flubromazepam (39 to 45). Thirty-eight (63.3%) sites were based in the UK/Europe. Drugs were sold as pellets (49 websites, 81.7%), powder (19, 31.7%), and blotters (1, 1.7%). Pill forms were not available, and one (1.7%) website sold diclazepam/flubromazepam in liquid form. The cost reduced with increasing purchase quantities. Main motivations for use included anxiolysis, management of benzodiazepine withdrawal, sedation/sleep aid, and management of stimulant withdrawal. CONCLUSIONS: These three benzodiazepines are widely available online, most commonly as pellets, and are (mis)used for a number of reasons. This study could be used to support triangulation of data from other sources to inform harm minimisation strategies.

Prevalence of Use of Electronic Nicotine Delivery Systems (ENDS) to Vape Recreational Drugs by Club Patrons in South London.

INTRODUCTION: Electronic nicotine delivery systems (ENDS, often called e-cigarettes) are nicotine delivery devices that heat nicotine into vapour that is inhaled, a process called 'vaping'. Use eclipsed nicotine-replacement therapy (NRT) in 2014 but ENDS role in smoking cessation remains controversial. Safety has not been proven and there have been reports to US poison centres regarding potential ENDS-related nicotine toxicity. A further concern is use of ENDS to vape recreational drugs, but there is limited data to substantiate this. The aim of this study was to report on ENDS use to vape recreational drugs in patrons of a South London nightclub where high prevalence of recreational drug use has previously been shown. METHODS: A convenience sample of 101 participants was surveyed in March 2015 as part of a larger survey on drug use. Individuals were asked if they used ENDS to vape nicotine and/or other substances (and if so which substances). RESULTS: Ninety (89.1 %) of respondents were male with median age of 28 years (IQR 23-34). Eighty (79.2 %) currently smoked cigarettes; 20 (19.8 %) currently used ENDS for nicotine. Six (5.9 %) reported using ENDS to take other substances: 2 for 'liquid cannabis' and 4 did not elaborate on the substance(s) used. Of these 6, 3 were using ENDS to vape nicotine and 3 had never used them for nicotine. CONCLUSION: 5.9 % of individuals in this sample reported using ENDS to vape substances other than nicotine. Further work is required in larger populations to determine how common this is, evaluate which agents are being vaped and to inform appropriate public education.

Analytical confirmation of synthetic cannabinoids in a cohort of 179 presentations with acute recreational drug toxicity to an Emergency Department in London, UK in the first half of 2015.

CONTEXT: Synthetic cannabinoid receptor agonists are the largest group of new psychoactive substances reported in the last decade; in this study we investigated how commonly these drugs are found in patients presenting to the Emergency Department with acute recreational drug toxicity. METHODS: We conducted an observational cohort study enrolling consecutive adult patients presenting to an Emergency Department (ED) in London (UK) January-July 2015 (6 months) with acute recreational drug toxicity. Residual serum obtained from a serum sample taken as part of routine clinical care was analyzed using high-resolution accurate mass-spectrometry with liquid-chromatography (HRAM-LCMSMS). Minimum clinical data were obtained from ED medical records. RESULTS: 18 (10%) of the 179 patient samples were positive for synthetic cannabinoid receptor agonists. The most common was 5F AKB-48 (13 samples, concentration 50-7600 pg/ml), followed by 5F PB-22 (7, 30-400 pg/mL), MDMB-CHMICA (7, 80-8000 pg/mL), AB-CHMINACA (3, 50-1800 pg/mL), Cumyl 5F-PINACA (1, 800 pg/mL) and BB-22 (1, 60 pg/mL). Only 9/18 (50%) in whom synthetic cannabinoid receptor agonists were detected self-reported synthetic cannabinoid receptor agonist use. The most common clinical features were seizures and agitation, both recorded in four (22%) individuals. Fourteen patients (78%) were discharged from the ED, one of the four admitted to hospital was admitted to critical care. CONCLUSIONS: Synthetic cannabinoid receptor agonists were found in 10% of this cohort with acute recreational drug toxicity but self-reported in only half of these. This suggests that presentations to the ED with acute synthetic cannabinoid receptor agonist toxicity may be more common than reported.

Acute Toxicity Associated with Use of 5F-Derivations of Synthetic Cannabinoid Receptor Agonists with Analytical Confirmation.

INTRODUCTION: Synthetic Cannabinoid Receptor Agonists (SCRAs) are the largest group of new psychoactive substances reported to the European Warning System and the United Nations Office on Drugs and Crime to date. The heterogeneous nature and speed of diversification of these compounds make it challenging to accurately characterise and predict harms of these compounds in pre-clinical studies, ahead of their appearance. CASE REPORT: We report the case of a 19-year-old female who purchased three products from a headshop: two new psychoactive substances (sachets of "cannabis tea" and "mushroom tea") as well as two LSD blotters. After the "cannabis tea" was smoked and the two LSD blotters and "mushroom tea" were ingested, the patient became tachycardic (HR 128), developed seizures, agitation, visual hallucinations as well as suspected serotonergic toxicity (sustained ankle clonus 20-30 beats) 1-2 hours after use. She was treated with 1 mg of intravenous midazolam. Symptoms/signs resolved within 13 hours. No further supportive care was required. Plasma, blood, and urine samples confirmed the presence of two SCRAs: 5FAKB-48 and 5F-PB-22. The patient also reported therapeutic use of both fluoxetine and citalopram for depression. DISCUSSION: To the best of our knowledge, this is the first case report of non-fatal intoxication with 5F-AKB-48 with analytical confirmation and exposure times. It also highlights the difficulties in understanding the pattern of toxicity of certain SCRAs in the context of psychotropic medications/co-morbid mental illness.