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.

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.

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.

Review article: Clinical manifestations and outcomes of chronic nitrous oxide misuse: A systematic review.

Recreational nitrous oxide (N2 O) use is widespread, and complications associated with its use are increasingly common. We sought to identify risk factors, clinical features and outcomes in individuals presenting with effects of chronic N2 O abuse to develop an approach to clinical assessment and management. A systemic literature review was completed with searches conducted across EMBASE, MEDLINE, PSYCINFO and Cochrane databases. Our search strategy identified 612 studies, 105 met inclusion criteria, and 10 were added via hand search. Subjects from 24 case series and 91 case reports were typically in their 20s, using over 100 bulbs daily for several months. Neurological presentations, including sensory change, gait disturbance or weakness, were characteristic. Serum Vitamin B12 was normal or raised in 133 out of 243 case series subjects and 37 out of 84 reports. Serum homocysteine and methylmalonic acid were usually raised. Macrocytosis and anaemia were not commonly seen. MRI findings were abnormal with dorsal column change where specified, typically involving the cervical spine. Nerve conduction studies mostly reported a sensorimotor polyneuropathy. B12 replacement was the treatment of choice and partial recovery was most reported. This review highlights the dose-dependent nature of chronic N2 O toxicity and recognises functional B12 deficiency as the cause. As B12 is often normal, homocysteine and methylmalonic acid are important biomarkers of disease. An approach to diagnosis is offered but requires validation in prospective studies. Research exploring B12 and methionine therapy is required to refine management.

Emergency department utilisation by patients with a diagnosis of borderline personality disorder: An acute response to a chronic disorder.

OBJECTIVE: Patients with borderline personality disorder (BPD) are likely to attend the ED while experiencing crises and associated self-injury and suicidality. Our study describes the prevalence, features, and outcomes associated with ED presentations by patients diagnosed with BPD in Outer Eastern Melbourne, Australia. METHODS: A retrospective electronic audit of 157 364 ED attendances identified 700 unique BPD-related ED presentations between May 2015 and April 2016. For the purpose of comparison, 583 (81% female) of these 700 cases were matched with 'depression only' cases. ED re-presentation data were also extracted. RESULTS: The 583 matched BPD patients attended ED a total of 2807 times during the audit year compared with 1092 attendances for matched depression-only patients. BPD patients were more likely to: arrive by ambulance (50%); have comorbid substance abuse (44%); have a psychotic (15%) or bipolar disorder (17%); be under the care of a psychiatrist (31%); be case-managed (42%); and be admitted to an inpatient unit (21%). ED doctors saw 38% of BPD or depression patients within the recommended time according to their triage category. The majority (73%) of BPD patients attended ED more than once during the audit year (average 4.81 ± 6.63 times; range 2-78). CONCLUSION: Repeated ED attendance of a subset of patients diagnosed with BPD highlights both the severity of their presentation and the inadequacy of community mental health services for meeting their complex needs. Development of effective ED referral pathways with follow-up to engage patients in BPD-appropriate treatment will reduce the likelihood of crises and reliance on hospital EDs for acute episodic care.

A cluster of 25B-NBOH poisonings following exposure to powder sold as lysergic acid diethylamide (LSD).

INTRODUCTION: 25B-NBOH is a synthetic hallucinogen closely related to the "NBOMe" family of N-substituted 2C phenethylamine derivatives. There have been no published reports documenting the clinical toxicity of NBOH derivatives. CASE SERIES: Five patients presented to the Emergency Department (ED) with altered conscious state following exposure to powder sold as "powdered LSD" at a party. A 24-year-old male who ingested the powder developed mydriasis, tachycardia, hypertension, and severe agitation requiring parenteral sedation. A 22-year-old male who insufflated the powder developed status epilepticus requiring intubation. Both patients developed acute kidney injury and one had rhabdomyolysis. In both cases, blood analysis detected 25-NBOH and no other illicit/licit drugs. Three other patients developed mild hallucinations. Hyperthermia was not documented in any case. DISCUSSION: Exposure to 25B-NBOH in a powdered form produced sympathomimetic toxicity, including hallucinations. Insufflation of 25B-NBOH led to rapid onset of status epilepticus in one case. Toxicity in all cases resolved within 12 h. Despite in vitro evidence of 5-HT2A receptor agonism, hyperthermia was not observed. Potent hallucinogens are often delivered via blotter paper to avoid excessive dosing. The severe clinical toxicity documented in these cases highlights the potential for development of adverse health effects with exposure to apparent small volumes of potent sympathomimetics.

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.

Treatment for beta-blocker poisoning: a systematic review.

Introduction: Beta-adrenoreceptor antagonist (beta-blocker) poisoning is a common overdose which can lead to significant morbidity and mortality.Objective: To evaluate the effects of treatments for beta-adrenoreceptor antagonist poisoning.Methods: Searches were conducted across MEDLINE (1946-26 November 2019, Ovid); Embase (1974-26 November 2019, Ovid); and the Cochrane Central Register of Controlled Trials (CENTRAL, to 26 November 2019) utilising a combination of subject headings and free text. The search strategy identified 15, 553 citations. Two reviewers screened titles and abstracts prior to selecting 141 articles (Kappa on articles included = 0.982, 95% CI 0.980-0.985). Primary outcomes included mortality and improvement in haemodynamic parameters (e.g., heart rate, blood pressure or a composite measure able to quantitate a haemodynamic response).Results: The risk of bias was high for all interventions.Gastric decontamination: Fifteen case reports described the administration of activated charcoal and five detailed the use of gastric lavage. As there was concurrent utilisation of multiple interventions, it was difficult to draw definitive conclusions regarding the relative contribution of these interventions to mortality or survival.Catecholamines, inotropes and vasopressors: The use of catecholamines in treating beta-blocker toxicity was reported in 16 case reports, 3 case series and 2 animal studies. These agents most likely provided a survival benefit and improved haemodynamics.Atropine: Multiple intravenous boluses of atropine were associated with improvement in heart rate and blood pressure in one case report.Calcium: Intravenous calcium was associated with an improvement in haemodynamics in three out of six case reports but in association with multiple other therapies as well as in two animal studies.High-dose insulin euglycaemic therapy: The use of this therapy was associated with mortality benefit in 10 case series. Two case reports showed clear haemodynamic improvement in a timeframe consistent with insulin administration (bolus then continuous infusion). Maintenance dosing ranged from 1 to 10 units/kg/h of insulin. However, it is unclear whether high-dose insulin euglycaemic therapy improved haemodynamic response above catecholamines and other inotropic agents in humans. Hypoglycaemia and hypokalemia were commonly observed adverse effects.Glucagon: Glucagon was associated with minor improvements in haemodynamics through an increase in heart rate in two cases series, nine case reports and five animal studies.Methylthioninium chloride (methylene blue): Four case reports reported an association with improvement in haemodynamics following administration of methylene blue but in the setting of co-ingestion with amlodipine.Intravenous lipid emulsion therapy: There was variable response to intravenous lipid emulsion therapy reported in 10 case series, 5 animal studies and 21 case reports.Lignocaine: There were four case reports showing variable response to lignocaine in arrhythmias secondary to beta-blocker toxicity.Other treatments: Fructose diphosphate, levosimendan and amrinone did not provide a mortality or significant haemodynamic benefit in three animal studies and nine case reports. .Veno-arterial extracorporeal membrane oxygenation: Veno-arterial extracorporeal membrane oxygenation was associated with improved survival in patients with severe cardiogenic shock or cardiac arrest in an observational study and four cases series.Dialysis: The evidence of four case reports suggest haemodialysis may assist in the management of massive overdose of specific water-soluble beta-blockers (e.g., atenolol) by improving elimination; however, a survival or haemodynamic benefit was not established.Pacing: One case series and a single case report showed the utility of temporary overdrive cardiac pacing to prevent arrhythmias in sotalol toxicity.Conclusions: Catecholamines, vasopressors, high-dose insulin euglycaemic therapy and veno-arterial extracorporeal membrane oxygenation were associated with reduced mortality. However, it must be acknowledged that multiple treatments were often given simultaneously. Haemodynamic improvements in blood pressure and cardiac output were seen with the use of catecholamines, vasopressin and high-dose insulin euglycaemic therapy. Evidence for treatment recommendations is almost entirely drawn from very low- to low-quality studies and subject to bias. However, it is reasonable to have a graduated response to cardiovascular instability beginning with intravenous fluids, commencement of a single or a combination of catecholamine inotropes and vasopressors depending upon the type of haemodynamic compromise (bradycardia, left ventricular dysfunction, vasodilation). High-dose insulin euglycaemic therapy can be introduced as an adjunctive inotrope and lastly, more invasive methods such as veno-arterial extracorporeal membrane oxygenation should be considered in cases unresponsive to other therapies.

End-tidal capnography provides reliable ventilatory monitoring for non-intubated patients presenting after sedative overdose to the emergency department.

OBJECTIVE: To assess the ability of end-tidal capnography to provide continuous ventilatory monitoring in sedated, non-intubated ED patients following sedative overdose. METHODS: Observational study undertaken in a tertiary hospital ED. Patient ventilation was assessed using capnography over 60 min. RESULTS: Capnography provided uninterrupted monitoring for 99% of total study time. Capnography detected all episodes of hypoxia detected by SpO2 monitoring. Changes in capnography preceded 70% of hypoxic episodes detected by SpO2 . There were no major adverse events or incidents of device failure. CONCLUSION: Capnography provided reliable measurement of ventilatory function in sedated non-intubated, poisoned ED patients.

Incidental hepatic steatosis in radiology reports: a survey of emergency department clinicians' perspectives and current practice.

INTRODUCTION: Hepatic steatosis is a relatively common incidental finding on computed tomography (CT) studies performed for patients in the emergency department (ED). The aim of our survey was to explore the preferences and perspectives of emergency physicians regarding reporting of incidental findings with a focus on hepatic steatosis. METHODS: A prospective web-based questionnaire was conducted and distributed electronically to emergency clinicians with anonymous collection of responses. RESULTS: A total of 236 responses were received. The true response rate could not be determined due to different methods of electronic distribution. However, there was an estimated representation of 8.3% for ED physicians and 2.5% for trainees. The median time spent on the survey was less than 3 minutes. Seventy-seven per cent answered yes to giving an incidental finding more significance if mentioned in the conclusion section. More than half of respondents (60.2%) reported that they would like hepatic steatosis to be mentioned in a CT report while 30% reported that it was irrelevant in the emergency setting and 10% reported that they did not want it mentioned in the report. The majority (83.1%) reported that they would include this finding in the discharge summary for GP follow-up and less than half (44.1%) would mention it to patients. CONCLUSION: Our survey highlights the importance of clear communication between radiologists and ED physicians when incidental findings are encountered. Radiologists play an important role in alerting ED physicians and clinicians who have access to patients' radiology reports to the presence of incidental findings including hepatic steatosis.

Incidental hepatic steatosis on unenhanced computed tomography performed for suspected renal colic: Gaps in reporting and documentation.

INTRODUCTION: Hepatic steatosis is a common incidental finding on computed tomography (CT) in patients presenting to the emergency department (ED). The aims of our study were to assess the prevalence of hepatic steatosis in ED patients with suspected renal colic and to assess documentation in radiology reports and medical charts correlated with alanine transaminase (ALT) levels. METHODS: Over 18 months from January 2016 to June 2017, all unenhanced CTs performed for suspected renal colic were reviewed. Quantitative assessment measuring hepatic and splenic attenuation in Hounsfield Units was performed. Hepatic steatosis was defined using multiple CT criteria including liver/spleen (L/S) ratio. Radiology reports, medical charts and ALT levels, if collected within 24 h of CT, were reviewed. RESULTS: A total of 1290 patients were included with a median age 52.5 years (range 16-98) and male predominance (835 [64.7%]). A total of 336 (26%) patients had hepatic steatosis measured by L/S ratio of ≤ 1.0. Ninety-four patients (28%) had radiology reports noting steatosis. Documentation in medical charts was noted in 18 of the 94 patients (19.1%) for whom steatosis was reported. Liver enzymes were available for 704 (54.6%) patients. There was a significantly higher mean ALT level in patients with hepatic steatosis (42.2 U/L; 95% CI 38.4-46.0) compared to patients without (28.8 U/L; 95% CI 25.7-31.9) (P < 0.0001). CONCLUSION: Our findings highlight multiple gaps in the reporting and evaluation of hepatic steatosis among radiologists and emergency clinicians alike. Recognising and reporting this incidental finding may impact health outcomes.

Aortic dissection detection risk score has high sensitivity with moderate inter-rater reliability.

OBJECTIVE: To retrospectively assess the accuracy and inter-rater reliability of the aortic dissection detection risk score (ADD-RS). METHODS: Single-centre, observational, diagnostic accuracy study undertaken in a university-affiliated, tertiary hospital ED. RESULTS: Two hundred patients were enrolled. Five patients were diagnosed with acute aortic dissection and had an elevated ADD-RS >0. The ADD-RS was 100% sensitive with a negative and positive predictive values of 100% (if ADD-RS ≥1). Inter-rater reliability was moderate (Kappa = 0.55). CONCLUSION: The ADD-RS was highly sensitive in our cohort. Further work to evaluate the score prospectively and in combination with a D-Dimer is required.

Taming the zebra: Unravelling the barriers to diagnosing aortic dissection.

Aortic dissection is a lethal cardiovascular emergency that continues to pose a diagnostic dilemma to the emergency physician. The condition is rare, can present atypically and is associated with a cumulative mortality for every hour that passes. While it is a recognised differential of acute chest pain, its prevalence in comparison to other causes often leads to the diagnosis being overlooked. The ED is a busy environment with high patient turnover and varying degrees of complexity and acuity. This increases susceptibility to cognitive bias and error-producing conditions that can lead to delayed or missed diagnosis. In reported cases where aortic dissection has been missed, clinician awareness of the disease was not the primary issue but failure to respond to clinical cues suggestive of aortic dissection was. To improve patient outcomes for this condition, it is important for clinicians to be aware of pertinent cognitive bias and error-producing conditions.