Protonitazene detection in two cases of opioid toxicity following the use of tetrahydrocannabinol vape products in Australia.

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 ß-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.

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.

Characteristics of First Nations patients who take their own leave from an inner-city emergency department, 2016-2020.

OBJECTIVE: Using a strength-based framework, we aimed to describe and compare First Nations patients who completed care in an ED to those who took their own leave. METHODS: Routinely collected adult patient data from a metropolitan ED collected over a 5-year period were analysed. RESULTS: A total of 6446 presentations of First Nations patients occurred from 2016 to 2020, constituting 3% of ED presentations. Of these, 5589 (87%) patients waited to be seen and 857 (13%) took their own leave. Among patients who took their own leave, 624 (73%) left not seen and 233 (27%) left at own risk after starting treatment. Patients who were assigned a triage category of 4-5 were significantly more likely to take their own leave (adjusted odds ratio [OR] 3.17, 95% confidence interval [CI] 2.67-3.77, P < 0.001). Patients were significantly less likely to take their own leave if they were >60 years (adjusted OR 0.69, 95% CI 1.01-1.36, P = 0.014) and had private health insurance (adjusted OR 0.61, 95% CI 0.45-0.84, P < 0.001). Patients were more likely to leave if they were women (adjusted OR 1.17, 95% CI 1.01-1.36, P = 0.04), had an unknown housing status (adjusted OR 1.76, 95% CI 1.44-2.15, P < 0.001), were homeless (adjusted OR 1.50, 95% CI 1.22-1.93, P < 0.001) or had a safety alert (adjusted OR 1.60, 95% CI 1.35-1.90, P < 0.001). CONCLUSION: A lower triage category is a strong predictor of First Nations patients taking their own leave. It has been documented that First Nations patients are under-triaged. One proposed intervention in the metropolitan setting is to introduce practices which expediate the care of First Nations patients. Further qualitative studies with First Nations patients should be undertaken to determine successful approaches to create equitable access to emergency healthcare for this population.

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.

Intoxications in an Australian Emergency Department Involving 'Nitazene' Benzylbenzimidazole Synthetic Opioids (Etodesnitazene, Butonitazene and Protonitazene).

Benzimidazole synthetic opioids are highly potent µ-opioid receptor agonists with heroin-like effects, including dose-dependent respiratory depression and a high risk of abuse and toxicity. Benzimidazoles were first detected in 2019 in Europe and Canada, with analytical confirmation of etodesnitazene, protonitazene and butonitazene in 2021. We report the first detections of these compounds in Australia, in two patients presenting with drug toxicity to Emergency Departments (EDs) in the state of Victoria. Case 1 was a female in her 20s who rectally administered etodesnitazene and was found unconscious with respiratory depression and hypotension. Case 2 was a female in her 30s who presented to the ED in a sedated state after taking a formulation of protonitazene that also contained butonitazene, in addition to methylamphetamine. She responded positively to naloxone. Novel synthetic opioids were used with prior experience of the formulations purchased; however, the unpredictability of their effects was demonstrated by the acute toxicity experienced with this occasion of use. Toxicosurveillance of ED presentations with analytical confirmation of drugs is crucial in identifying emerging drugs in the community and informing harm reduction strategies.

Characteristics, presentation and outcomes of music festival patrons with stimulant drug-induced serotonin toxicity.

OBJECTIVE: A large number of stimulant drug-associated deaths at music festivals in Australia were reported during the southern hemisphere summer of 2018-2019. This led to the prehospital deployment of healthcare professional-led critical care response teams. We aimed to describe the characteristics, clinical presentation, management and outcomes of music festival patrons with stimulant drug-induced serotonin toxicity managed using this model during the study period. METHODS: We performed a retrospective observational study of patients presenting with stimulant drug-induced serotonin toxicity and/or drug-induced hyperthermia who presented between December 2017 and December 2019. Comprehensive follow-up data were collected for those patients who required hospital admission. Data included demographics, clinical features, management and disposition, hospital outcomes and laboratory data, stratified by severity of presentation. RESULTS: Forty-seven patients were included. Median age was 21.9 years (interquartile range 19.6-22.2). 3,4-Methylenedioxymetamphetamine was the most frequently reported agent ingested (32/47). After stratification, 13 of 47 patients were classified as mild, 20 of 47 as moderate and 14 of 47 as severe. Median presenting temperature in this latter cohort was 41.1°C (40.5-42.0°C). All severely ill patients required intensive care unit admission, with a median hospital stay of 4.63 days (interquartile range 2.08-8.36). End-organ complications were reported in 11 of 14 patients. No mortalities were reported. All patients (13/13) from the mild cohort and 15 of 20 patients from the moderate cohort were treated and discharged on-site. CONCLUSIONS: Severe illness was associated with a high incidence of end-organ impairment. A high proportion of patients without severe disease were able to be successfully managed at the event without transport to hospital. No deaths are reported in this series.