Toxicological and Clinical Characteristics of Fatal Cases in the Emerging Drugs Network of Australia—Victoria ( EDNAV ) Clinical Registry 2020–2025

ABSTRACT Objective The objective of this study is to characterise the analytical toxicology findings and clinical features of fatal cases recorded in the Emerging Drugs Network of Australia—Victoria (EDNAV) clinical registry. Methods EDNAV is a state‐wide toxicosurveillance system capturing de‐identified demographic, clinical and analytical data from ED presentations with illicit drug‐related toxicity. Venous blood samples are screened for illicit, pharmaceutical and novel psychoactive substances (NPS) using liquid chromatography–quadrupole time‐of‐flight mass spectrometry. We conducted a retrospective observational case series of fatal registry cases recorded between September 2020 and December 2025. Results Forty‐six fatal cases were identified (0.9% of 5026 EDNAV cases). Most patients were male (89%) with a median age of 33 years. Out‐of‐hospital cardiac arrest occurred in 67% of cases. Polysubstance exposure predominated (91%), with a median of three substances detected per case. Mixed stimulant–sedative patterns were most common (64%), followed by opioid–benzodiazepine (19%) and stimulant‐only (7%). The most frequent individual detections were methamphetamine (54%), heroin (52%), diazepam (37%), cocaine (20%) and MDMA (17%). NPS accounted for 7.8% of detections, were never identified in isolation and were predominantly novel benzodiazepines (80%). Hypoxic brain injury was the most common terminal complication (72%). Conclusion Fatal cases were characterised by near‐universal polysubstance detections, with methamphetamine and heroin the most frequent individual detections. Most deaths occurred out of hospital, with many patients presenting with irreversible hypoxic brain injury. NPS were rare and co‐occurred with traditional illicit substances. Community‐based interventions including bystander resuscitation, early emergency service activation and take‐home‐naloxone represent the highest‐yield strategies to reduce mortality from illicit substance use in Victoria.