Rapid detection, toxicosurveillance and public health response to stimulant adulteration with acetyl fentanyl

To the Editor: We identified a geographic and temporal cluster of four patients with drug poisoning occurring within one week in February 2020 from two addresses less than 1 km apart. All patients presented with typical features of opiate poisoning but had no history of opiate use. There was one death, with the three other cases having significant morbidity, which required escalating bolus doses of naloxone.

Rapid sample analysis by the New South Wales Pathology Forensic and Analytical Science Service (FASS) using liquid chromatography quadrupole time‐of‐flight mass spectrometry (LC‐Q‐TOF‐MS) found acetyl fentanyl — a synthetic fentanyl non‐pharmaceutical designer drug — in all cases within 3 days. The identification and subsequent response were coordinated by the Prescription, Recreational and Illicit Substance Evaluation (PRISE) program, a collaboration between the NSW Ministry of Health, the NSW Poisons Information Centre and FASS. The analytical confirmation and public health response, involving data collection, risk assessment with a health expert committee and customised clinical and public health response, occurred within 15 days of notification to PRISE. Two further cases were identified by the NSW Ministry of Health in other hospitals in the 2 months prior and 2 months subsequent to our cases. In October 2020, a further cluster of five cases occurred in regional NSW.

Ethics approval was granted by the Sydney Local Health District Research Ethics and Governance Office, HREC 2020/ETH01380.

The presence of fentanyl analogues as an adulterant in recreational drugs has become common globally but only one case of poisoning by acetyl fentanyl has been reported in the literature in Australia.1,2 This poses a significant risk to unassuming users, particularly users whose primary recreational use is stimulants, as they are likely to be opioid naïve and have worse clinical outcomes. Cases of toxicity from fentanyl and its analogues are often under‐reported because of issues with detection. Synthetic opioids do not test positive on urine drug screen immunoassays; mass spectrometry is required to confirm the diagnosis.3

Acetyl fentanyl is a non‐pharmaceutical designer analogue of fentanyl first described in 2013 after an outbreak with reported mortality in Rhode Island.4 Pharmacokinetic data for acetyl fentanyl are limited, but the drug is 15 times more potent than heroin and has an ED50 (median effective dose) and LD50 (median lethal dose) ten times narrower than morphine.5

The purpose of PRISE is to detect atypical substances in the community, focusing on presentations that are unexpected, severe and/or clusters, and coordinate an appropriate response. Rapid detection and toxicosurveillance allowed for prompt dissemination of information to clinicians and the public. Information directed to user groups is a particularly important harm minimisation strategy.

Rapid detection and early dissemination of information may have limited further outbreaks. Clinicians should be informed that atypical presentations in recreational drug use may be due to substitution or contamination by other substances. Notification of cases to Poisons Information Centres can provide treatment advice and facilitate rapid identification and response by providing an access pathway, such as the NSW Ministry of Health PRISE Program.