Emergency Department Patients with Para-Fluorofentanyl Overdose

Background: Fentanyl analogs, such as para-fluorofentanyl (PFF), are increasing in the illicit opioid supply. Objectives: This study characterizes demographics, clinical effects, and sex differences for naloxone administration in emergency department (ED) patients with confirmed PFF overdose compared with fentanyl. Methods: This prospective observational cohort is from the ToxIC Fentalog Study between 2020 and 2023 at 10 participating U.S. hospitals. Adult patients with suspected opioid overdose presenting to EDs were screened and eligible if waste serum samples were available for comprehensive toxicological analysis. Fentanyl-positive patients were included in this analysis examining associations between PFF and naloxone administration, with stratified analyses for sex differences. Results: Of 4873 screened, 833 were included; 694 PFF negative (PFFN) and 139 PFF positive (PFFP). Mean age was 41 years, and men were predominant (PFFN 73.1% vs. PFFP 69.8%). More than half of PFFP patients presented at 2 of the 10 participating sites, New York (29.8%) and Pennsylvania (21.3%). The most common indication for naloxone was depressed level of consciousness (PFFN 82.1% vs. PFFP 79.8%). PFFP were less likely to receive naloxone doses > 2 mg compared with PFFN (48.2% vs. 60.8%, p = 0.002). After controlling for covariates, PFFP were less likely to receive out-of-hospital naloxone (adjusted odds ratio 0.87; 95% confidence interval 0.81–0.94). PFFP men were less likely to receive naloxone doses ≥ 2 mg (adjusted odds ratio 0.64; 95% confidence interval 0.42–0.97), but this association was not significant for women. Conclusion: PFF was present in almost 20% of ED patients with confirmed fentanyl overdose. Although naloxone administration was lower for PFF compared with fentanyl, differences were more pronounced in men. Clinicians and public health officials should be aware of the evolving illicit opioid supply. Future study is warranted to explore the PFF dose response and mechanism behind these observed sex differences due to fentanyl analogs.