Xylazine Testing and Withdrawal for the CL Psychiatrist: A Retrospective Cohort Study and Clinical Primer

Abstract:

Background: Xylazine is an alpha-2 agonist and common fentanyl adulterant, present in 23% of fentanyl powder samples and found in 48 states (DEA, 2023). Xylazine-contaminated fentanyl was declared an emerging threat in 2023 (WHONDCP, 2023) yet little is known about human urine testing for xylazine and if there is a unique xylazine withdrawal syndrome that merits specific treatment.



Methods: We analyzed electronic health record data for adults with gas chromatography-mass spectrometry (GC-MS) xylazine testing performed at 3 academic hospitals in Philadelphia, PA from 3/2022-2/20223. We described xylazine testing results and specimen collection times. Four addiction experts identified possible xylazine withdrawal symptoms among xylazine-positive cases based on vital signs, physical exam findings, and patient-reported symptoms.



Results: Of 128 GC-MS urine xylazine tests performed, 73 (57.0%) were positive. Xylazine-positive samples were collected earlier (mean time from Emergency Department [ED] presentation to specimen collection 8.3 hours [SD 9.0] vs. 27.2 hours [SD 62.8]; p=0.012). Of samples obtained within 48 hours, faster collection time was not associated with likelihood of a positive result (p=0.178). The longest time from ED presentation to positive specimen collection was 42.9 hours. Xylazine-positive charts demonstrated high variability in documented symptoms. Expert review for xylazine withdrawal symptoms found 52 patients (71.3%) with no sign of a distinct withdrawal syndrome, 19 patients (26.4%) with possible withdrawal syndrome, and 2 patients (2.7%) with a likely withdrawal syndrome. Xylazine-positive patients were less likely to need ICU care (15 of 73 [20.5%] vs. 27 of 55 [49.1%], p=0.001).



Discussion: While some physicians are familiar with signs and symptoms of xylazine use, this study is among the first to examine xylazine testing in humans with chronic use and their associated withdrawal symptoms. Though xylazine is found in >90% of fentanyl samples in Philadelphia (CFSRE, 2022), < 60% of patients tested positive for xylazine. No positive specimens were found beyond 43 hours, suggesting that human renal clearance of xylazine is approximately two days. We did not detect a distinguishable xylazine withdrawal syndrome using xylazine-positive urine to differentiate patients. It is therefore questionable if patients using xylazine-contaminated fentanyl require specific, versus more aggressive, pharmacologic management. Despite concerns that xylazine contamination may be more dangerous in an overdose due to lack of response to naloxone, patients were less likely to require ICU care.



Conclusion: Human renal clearance of xylazine appears to be approximately 2 days and therefore urine specimens should be collected within this time frame when using GC-MS testing. Among xylazine-positive patients, no distinct withdrawal syndrome was identified, suggesting that more aggressive rather than unique pharmacologic management strategies may be most appropriate.



References:

1. DEA Public Safety Alert, “DEA Reports Widespread Threat of Fentanyl Mixed with Xylazine.” March 20, 2023. https://www.dea.gov/alert/dea-reports-widespread-threat-fentanyl-mixed-xylazine

2. White House Office of National Drug Control Policy. Biden-Harris Administration Designates Fentanyl Combined with Xylazine as an Emerging Threat to the United States. April 12, 2023. https://www.whitehouse.gov/ondcp/briefing-room/2023/04/12/biden-harris-administration-designates-fentanyl-combined-with-xylazine-as-an-emerging-threat-to-the-united-states/

3. CFSRE - NPS Discovery, “Drug Checking Quarterly Report (Q3 2022): Philadelphia, Pennsylvania, USA.” November 21, 2022. https://www.cfsre.org/nps-discovery/drug-checking/drug-checking-q3-2022-philadelphia-pennsylvania-usa



Presentation Eligibility: Previously presented at Society for General Internal Medicine by AP Thakrar. It is unlikely that ACLP attendees also attended SGIM. Results are unpublished and otherwise unavailable. The presentation will include results of the study as well as additional information on clinical presentation and management in our ongoing experience.

Diversity, Equity, and Inclusion: Patients with substance use disorders face significant stigma, even within psychiatry. They often receive highly inequitable care in general medical hospitals and are disproportionately impacted by patient directed discharges. This study aims to fill gaps in diagnosis and treatment for patients using xylazine, who are too often labeled in the media as subhuman "zombies." This presentation re-humanizes these patients and presents them as worthy of research, clinical attention, and care.