Managing Patients Taking Xylazine-Adulterated Opioids in Emergency, Hospital, and Addiction Care Settings



Meeting Summary

In response to the rapid escalation in the detection of xylazine in the unregulated drug supply, in April 2023, the White House designated fentanyl contaminated with xylazine an "emerging threat". The National Institute on Drug Abuse (NIDA) Center for the Clinical Trials Network (CCTN) convened health care professionals and federal partners to review current practices in xylazine-related testing, treatment, and wound care to inform evolving best-practices in the field. This convening focused on the most critical areas of concern with the goal of rapidly identifying current practices and a xylazine-opioid research agenda.

Welcome and Opening Remarks

The meeting is opened by NIDA Director Nora Volkow, M.D., with welcoming remarks from CCTN Director Betty Tai, Ph.D., and CCTN Associate Director, Kristen Huntley, Ph.D. The two meeting co-chairs—Jeanmarie Perrone, M.D., University of Pennsylvania, and Rachel Haroz, M.D., Cooper Medical School of Rowan University—who helped shape the agenda and identify experts on the topic, also provided introductory remarks.

Session 1: Pharmacology and Clinical Manifestations of Withdrawal and Overdose

Presenters focus on current knowledge of xylazine’s pharmacology, clinical outcomes of xylazine-exposed patients who present in the emergency department (ED), and the signs and symptoms of xylazine withdrawal—as well as their treatment.

  • Xylazine Pharmacology
    Joseph D’Orazio, M.D., Temple University School of Medicine and Giacomo Gianotti, D.V.M., D.V.Sc., DACVAA, University of Pennsylvania School of Veterinary Medicine
    Dr. D’Orazio explains how xylazine decreases sympathetic nervous system outflow, causes sedation, and produces other physiological effects. When fentanyl and xylazine are combined, naloxone should be provided per the usual protocol when an opioid overdose is suspected.
  • Xylazine Withdrawal, Opioid Withdrawal, and Medication Induction
    Matthew Salzman, M.D., Cooper Medical School of Rowan University
    Dr. Salzman describes his clinical experience managing withdrawal and notes the challenge of not knowing the relative concentrations of fentanyl and xylazine in the drugs patients have taken. The complete xylazine withdrawal syndrome is not clear, and some patients report that that their xylazine withdrawal is not adequately treated.
  • Opioid Overdoses Involving Xylazine in Emergency Department Patients: A Multicenter Study
    Jennifer Love, M.D., Icahn School of Medicine at Mount Sinai
    Dr. Love discusses a multicenter cohort study to investigate the effects of xylazine on the clinical outcomes of ED patients with a suspected opioid overdose. Results indicated that after adjusting for relevant characteristics, patients positive for xylazine had lower odds of cardiac arrest and coma within 4 hours compared to those with only opioids. 
  • Manifestations of Xylazine and Fentanyl Withdrawal in a Hospital Cohort
    Maggie Lowenstein, M.D., M.S.H.P., and Ashish Thakrar, M.D., University of Pennsylvania Perelman School of Medicine
    Dr. Lowenstein reviews a study on xylazine withdrawal, commenting that symptoms (e.g., anxiety, restlessness, and discomfort) varied greatly and that most patients had good outcomes with treatment. Dr. Thakrar discusses a study in Philadelphia, which estimated that the duration of xylazine in urine samples was less than 24-48 hours.

Session 2: Xylazine Wounds 

Little is understood about xylazine wounds (generally seen on the arms and legs) or satellite wounds (i.e., distinct injuries not at an injection site). Presenters describe how care is being provided for patients in the community—as individuals with open wounds are often turned away from inpatient drug treatment centers and shelters—and surgical management over the long term.

  • Hands On: Care Provided in the Community
    Stephanie Klipp, R.N., CARN, CAAP, CRS, Courage Medicine
    Ms. Klipp explains that in Philadelphia, most xylazine-exposed individuals are unhoused and have difficulty accessing regular wound treatment and keeping the necessary self-care supplies. In addition to describing wound treatment, Ms. Klipp points out the need for updated hospital protocols, low-barrier wound care, training on this topic, stigma reduction, and substance use treatment.
  • Surgical: Managing Complex Wounds Long-Term
    Lisa Rae, M.D., Temple Burn Center
    Xylazine wounds are necrotizing soft tissue wounds that feature a unique pattern not seen with heroin-related wounds. Dr. Rae notes that her approach is moving away from aggressive excision (typically the first-line treatment), outlines key clinical and research questions, discusses the unique characteristics of satellite wounds, and reviews harm reduction strategies to reduce operative interventions and help avoid amputation.

Session 3: Testing 

Commercial testing of the illicit drug supply has increased significantly, which raises many questions. Speakers discuss how patients view the usefulness of xylazine tests, a state-wide program that checks the illicit drug supply, and a research collaborative for drug testing with rapid sharing of results.

  • Patient Perspectives and Utility of Xylazine Test Strips
    Megan K. Reed, Ph.D., M.P.H., Department of Emergency Medicine, Thomas Jefferson University
    Dr. Reed discusses the results of two qualitative research studies with people who use drugs, focusing on (1) practices related to fentanyl test strips on non-heroin drugs and (2) responses to xylazine. She explains study participants’ concerns about fatal overdose, desire for test strips, dislike of the sensations associated with xylazine exposure, and experiences of withdrawal.
  • State-wide Drug Testing in Rhode Island: Xylazine
    Rachel Wightman, M.D., Alpert Medical School of Brown University and Rhode Island Department of Health
    Dr. Wightman reviews Rhode Island’s drug testing program which rapidly disseminates results to inform harm reduction efforts. She notes that xylazine is always detected in the presence of fentanyl. She stresses the need for research on xylazine’s pharmacokinetics, the development of an integrated testing infrastructure, and qualitative information to interpret and contextualize the results of quantitative testing. 
  • Xylazine Testing for Harm Reduction and Clinical Care
    Edward R. Sisco, Ph.D., National Institute of Standards and Technology
    Dr. Sisco explains NIST’s work with Johns Hopkins to evaluate xylazine test strips. The Rapid Drug Analysis and Research program tests samples for drugs within 24 to 48 hours and sends results back within 5 minutes. Dr. Sisco reviews the program’s process, results to date, and future work. 

Roundtable Discussion and Wrap Up

Drs. Perrone, Haroz, and Thakrar lead a discussion in which participants generate several high-priority research questions in the areas of (1) pharmacology and clinical manifestations of withdrawal and overdose, (2) xylazine wounds, and (3) testing. Aidan Hampson, Ph.D., describes NIDA’s Notice of Special Interest (NOSI), Xylazine: Understanding its Use and the Consequences (NOT-DA-24-009). The purpose of the NOSI is to encourage research on the prevalence and consequences of xylazine use, as well as its treatment—including overdose alone or in combination with other drugs.

Closing Remarks

Drs. Volkow and Perrone thank participants for a rich discussion and Dr. Huntley expresses gratitude to the meeting co-chairs for their work, especially the identification of experts on this topic.

Full Agenda - Xylazine Meeting Agenda (PDF, 254KB)