ACMT Toxicology Visual Pearl: Needle to Necrosis

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.