Xylazine Toxicity

Aka: Xylazine Toxicity, Xylazine, Horse Tranquilizer, Tranq Dope

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II. Mechanism

  1. Alpha 2 Adrenergic Agonist (similar to Clonidine, Dexmedetomidine) with central acting decrease in sympathetic tone
    1. Acts at imidazoline receptor (Hypotension, Bradycardia)
    2. Acts at a2 Adrenergic Receptor (sedation)
    3. Used as a Sedative, Analgesic and centrally acting Muscle relaxant in veterinary medicine
    4. Has been studied in humans as a Sedative agent, but not approved due to serious adverse effects
  2. Like Xylazine, Medetomidine is another Alpha 2 Adrenergic Agonist starting top be found in street Opioids
    1. Medetomidine is a racemic mixture (Dexmedetomidine, levomedotomidine) used in veterinary medicine
  3. Street name, "Horse Tranquilizer", added to injection Drugs of Abuse (e.g. Fentanyl, Cocaine) to enhance euphoria
    1. Xylazine is typically combined with potent Opioids (esp. Fentanyl), with which it has synergistic effects
      1. Combination of Xylazine and Fentanyl is referred on street as "Tranq Dope" (or tranq)
      2. Appears to enhance, speed onset and lengthen duration of opioid Sedative effects
      3. May also be found combined with Cocaine or Methamphetamine
    2. Added to ilicit opiods since ~2005 (Puerto Rico, Philadelphia) and is now found in many U.S. samples
    3. Associated with Opioid Overdose deaths, and unresponsive to Naloxone
      1. Frequently found in postmortem lab testing in Opioid deaths

III. Pharmacokinetics

  1. Typically injected, but is also well absorbed with ingestion, inhalation and via intranasal route
  2. Half-Life: 5 hours after injection
  3. Duration: 4 to 8 hours
  4. Symptoms manifest with as little as 10 mg injected

IV. Findings

  1. Overdose unresponsive to Naloxone
  2. Neurologic
    1. Pupil Constriction (Miosis)
    2. Sedation
    3. Respiratory Depression
  3. Cardiovascular
    1. Bradycardia
    2. Hypotension (may follow initial Hypertension)
  4. Endocrine
    1. Hyperglycemia (mild)
  5. Skin
    1. Open Skin Ulcerations (and later necrotic Skin Wounds) at injection site
      1. Most frequently found on the extensor surface of extremities
      2. Onset as dark bullae at injection site over otherwise intact skin
      3. Bullae coalesce into a large lesion that ulcerates over days
      4. Black eschar may develop over ulcer
      5. Ulcers may be deep enough to expose Muscles, tendons and bone
    2. Unique Skin Wound causes are not fully understood
      1. Local Vasoconstriction and tissue Hypoxia
      2. Pressure Ulceration due to prolonged immobility
      3. Poor Wound Healing due to debilitated state
      4. Direct cytotoxic effects of Xylazine
      5. Drug-Induced Vasculitis (due to Xylazine or other injected co-agents)

V. Labs

  1. See Unknown Ingestion
  2. Bedside Glucose
  3. No drug levels are available

VI. Diagnostics

  1. Electrocardiogram

VII. Management

  1. See Unknown Ingestion
  2. Decontamination
    1. Consider Activated Charcoal if large ingestion within prior hour and protected airway
  3. Respiratory depression
    1. Monitor with both Capnography (apnea) and Oxygen Saturation
    2. Naloxone for Opioid coingestion reversal
      1. Give Naloxone in all suspected Opioid-induced respiratory arrests (even if coingested)
      2. Fentanyl (of the Fentanyl-Xylazine combination) is more likely to cause severe respiratory depression
      3. Use the lowest Naloxone dose that maintains adequate spontaneous respiration (prevent withdrawal)
      4. Xylazine is NOT reversed with Naloxone, and has no known antidote
        1. However Atipamezole, Yohimbine and tolazoline have been studied for reversal in animals
    3. Endotracheal Intubation if indicated
    4. Supplemental Oxygen
  4. Symptomatic Bradycardia
    1. Atropine
  5. Hypotension
    1. Intravenous Fluids
    2. Norepinephrine
  6. Significant Ventricular Dysrhythmia
    1. Amiodarone
    2. Lidocaine
  7. Substance Withdrawal
    1. Xylazine withdrawal may cause anxiety, restlessness and cravings
      1. However, withdrawal treatment is primarily directed at other substances (see below)
      2. Refractory Xylazine withdrawal may respond to Tizanidine, Lofexidine, Guanfacine or Clonidine
    2. Opioid Withdrawal may present with Mydriasis, Yawning, Vomiting and Diarrhea
      1. See Opioid Withdrawal
      2. See Clinical Opioid Withdrawal Scale (COWS)
      3. See Opioid Withdrawal Management with Buprenorphine
    3. Alcohol Withdrawal may present with Tremor, Tachycardia, Hypertension, Hallucinations and Seizures
      1. See Alcohol Withdrawal
    4. Benzodiazepine Withdrawal may present similarly to Alcohol Withdrawal
      1. See Benzodiazepine Withdrawal
  8. Wound Care of ulcerative lesions
    1. Evaluate for underlying abscess, foreign body, Cellulitis and Sepsis
    2. Wound Debridement of nonviable tissue (e.g. Wet-to-Dry Dressings)
  9. Disposition
    1. Admit all symptomatic patients (e.g. Symptomatic Bradycardia, Hypotension)
    2. May discharge if asymptomatic at 4 to 6 hours from use
  10. Discharge Instructions
    1. See Opioid Use Disorder
    2. Prescribe home Naloxone
    3. Offer Buprenorphine For Opioid Withdrawal

VIII. References

  1. Spadaro, Perrone, Nelson and Greller (2025) Crit Dec Emerg Med 39(5): 30-7
  2. Tomaszewski (2022) Crit Dec Emerg Med 36(6): 32

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