Evaluating the Impact of Fentanyl Immunoassay Cutoff Concentrations in Emergency Department, Maternal, and Neonatal Populations

Qualitative urine drug screens (UDSs) are essential in clinical toxicology for assessments of drug exposure and are commonly employed by emergency departments to provide rapid results that inform care. Fentanyl, a potent synthetic opioid, is of significant public health concern due to rising overdose rates. However, fentanyl is also administered clinically as an analgesic, which may result in positive UDS assessments for patients with iatrogenic exposure. Positive UDS findings may cause patient anxiety, provider confusion, and lead to medicolegal concerns in clinical settings such as labor and delivery and neonatology. As such, it is essential that UDSs are utilized appropriately and that the positivity threshold for the assay is rigorously evaluated to serve the clinical need. This study examined UDS utilization within a quaternary care system over a one-year period. A subset of remnant urine specimens from UDSs were further analyzed using HRMS (high resolution mass spectrometry) and LC-MS/MS (liquid chromatography-tandem mass spectrometry) to focus on the impact of fentanyl immunoassay cutoff concentrations in high-volume populations. At our institution, the adult emergency department (ED) had the highest number of specimens ordered (5,901), while neonatal units had the least (727). Notably, fentanyl positivity rates were the highest in neonatal units at 34%. Quantitative analysis of remnant urine samples from the ED, labor and delivery (L&D), and neonatal units showed higher fentanyl concentrations in the ED, indicative of illicit use, and lower concentrations in L&D and neonates, consistent with analgesic administration. Raising the immunoassay cutoff from 1.0 ng/mL to 5.0 ng/mL would convert iatrogenic positives to negatives while retaining illicit positives. These findings underscore the need to evaluate UDS cutoff values for improved clinical performance in different populations.