xylazine skin necrosis

Which of the following agents, when injected along with heroin, is associated with the skin changes pictured?

  1. Cocaine
  2. Fentanyl
  3. Methamphetamine
  4. Xylazine

Photo by Dr. Matthew Salzman

4. Xylazine

Background

Xylazine is a synthetic substance approved by the U.S. Food and Drug Administration for veterinary use, specifically for its muscle relaxant, sedative, and analgesic effects [1]. Recently, xylazine has gained attention in the media with increasing reports of xylazine-related overdose deaths in patients. When combined with illicit opioids such as heroin and fentanyl, xylazine may increase the risk of fatal overdose given the augmented sedation and respiratory depression effects [2]. Xylazine use is also associated with severe necrotic skin ulcerations and superimposed infection [3, 4].

How does xylazine toxicity present?

  • Xylazine is an alpha-2 agonist similar to clonidine that inhibits the release of norepinephrine and epinephrine resulting in decreased vascular tone and heart rate [4].
  • Xylazine is often added to other illicit agents such as heroin. Like opioid intoxication, xylazine exposure may result in [4]:
    • Respiratory depression
    • Bradycardia
    • Miosis
    • Hypotension
    • CNS depression
  • Skin findings from chronic use range from superficial ulcerations and cellulitis to severe soft tissue destruction either at or distant from the IV injection sites. The skin changes are thought to be secondary to xylazine’s vasoconstricting properties on local blood vessels resulting in decreased skin perfusion, impaired wound healing, and increased risk of infection [5].
  • Dependence may occur from chronic use, and cessation of xylazine may present with withdrawal symptoms such as [4, 6, 7]:
    • Dysphoria
    • Agitation
    • Hypertension
    • Tachycardia
    • Diaphoresis
  • Other less-commonly observed adverse effects [8]:
    • Ataxia
    • Dysarthria
    • Hypotonia
    • Urinary incontinence
  • In a multicenter cohort study, ED patients with illicit opioid overdose who tested positive for xylazine were less likely to suffer cardiac arrest and coma [9].

How do you treat xylazine toxicity?

  • Treatment consists of supportive care, ranging from IV fluids to mechanical ventilation in patients with severe respiratory depression [10].
  • Naloxone will not reverse the effects of xylazine; however, it is routinely given in unresponsive or obtunded patients presenting with an opioid toxidrome. In patients with minimal response to naloxone, xylazine toxicity may be suspected [10].
  • In patients with skin changes, consider topical wound care as well as further evaluation of deep tissue infections, osteomyelitis, and ischemia. Patients may need admission for IV antibiotics, debridement, and specialty evaluation [8].
  • Chronic xylazine use and withdrawal is not well-defined; however, there is a case report of managing xylazine withdrawal with dexmedetomidine, tizanidine, and phenobarbital then later transitioning to clonidine [6].

Bedside Pearls

  • When xylazine is combined with other opioids, respiratory depression, sedation, hypotension, and bradycardia may be augmented and not responsive to naloxone.
  • Consider xylazine co-intoxication if a patient presenting with an opioid toxidrome has persistent sedation despite escalating naloxone administration.
  • Chronic use of xylazine via injection can lead to the development of ulcerations and severe soft tissue destruction, often with superimposed infection, requiring wound care and IV antibiotics.
  • Treatment for toxicity involves supportive care.

References

  1. Drug Enforcement Administration. Xylazine. Drug & Chemical Evaluation Section. Published May 2023. Available at: Xylazine (usdoj.gov)
  2. Kariisa M, Patel P, Smith H, Bitting J. Notes from the Field: Xylazine Detection and Involvement in Drug Overdose Deaths – United States, 2019. MMWR Morb Mortal Wkly Rep. 2021;70(37):1300-1302. Published 2021 Sep 17. PMID: 34529640
  3. Ayub S, Parnia S, Poddar K, et al. Xylazine in the Opioid Epidemic: A Systematic Review of Case Reports and Clinical Implications. Cureus. 2023;15(3):e36864. Published 2023 Mar 29. PMID: 37009344
  4. Gupta R, Holtgrave DR, Ashburn MA. Xylazine – Medical and Public Health Imperatives. N Engl J Med. 2023 Jun 15;388(24):2209-2212. Epub 2023 Apr 26. PMID: 37099338.
  5. Ruiz-Colón K, Chavez-Arias C, Díaz-Alcalá JE, Martínez MA. Xylazine Intoxication in Humans and Its Importance as an Emerging Adulterant in Abused Drugs: A Comprehensive Review of the Literature. Forensic Sci Int. 2014;240:1-8. Published 2014 Mar 26. PMID: 24769343
  6. Ehrman-Dupre R, Kaigh C, Salzman M et al. Management of Xylazine Withdrawal in a Hospitalized Patient: A Case Report. Journal of Addiction Medicine 16(5):p 595-598, 9/10 2022. PMID: 35020700
  7. Knopf, A. Effects of Xylazine in Illicit Fentanyl Supply: Report from OASAS. Alcoholism & Drug Abuse Weekly. 2023;35(26):6-7. Published 2023 June 30. DOI
  8. Malayala SV, Papudesi BN, Bobb R, Wimbush A. Xylazine-Induced Skin Ulcers in a Person Who Injects Drugs in Philadelphia, Pennsylvania, USA. Cureus. 2022;14(8):e28160. Published 2022 Aug 19. PMID: 36148197
  9. Love JS, Levine M, Aldy K, et al. Opioid overdoses involving xylazine in emergency department patients: a multicenter study. Clin Toxicol (Phila). 2023 Mar;61(3):173-180.. PMID: 37014353
  10. Ball NS, Knable BM, Relich TA et al.. Xylazine Poisoning: A Systematic Review. Clinical Toxicology, 60:8, 892-901. Published 2022 Apr 20. PMID: 35442125
Christiana Agbonghae, MD

Christiana Agbonghae, MD

Emergency Medicine Resident
Carolinas Medical Center
Christiana Agbonghae, MD

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Ann-Jeannette Geib, MD

Ann-Jeannette Geib, MD

Medical Toxicologist Faculty
Department of Emergency Medicine
Carolinas Medical Center, Charlotte, NC