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#392 Live! Opioid and Xylazine Withdrawal in the Hospital

April 26, 2023 | By


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Dominate opioid and xylazine (aka tranq) withdrawal in the hospital with expert insights from Dr. Joseph D’Orazio (@dorazepam) recorded LIVE! at Pennsylvania Hospital Grand Rounds in Philadephia, PA. Xylazine, an alpha-2 adrenergic agonist,  has emerged as a frequent contaminant in the opioid supply with a distinct withdrawal syndrome. You’ll learn to manage this common withdrawal syndrome while also addressing acute pain complaints and opioid withdrawal.  

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Show Segments

  • Intro
  • Xylazine basics
  • Management of xylazine withdrawal
  • Opioid withdrawal and acute pain
  • Outpatient considerations for xylazine
  • Audience questions
  • Outro

Opioid and Xylazine Withdrawal Pearls

  1. Xylazine (aka tranq) is an alpha-2 adrenergic agonist commonly found as an adulterant of fentanyl
  2. Recognize xylazine withdrawal in the patient on an adequate regimen for opioid withdrawal who has residual anxiety/restlessness
  3. Recognize xylazine withdrawal in the patient with an overdose who does not respond to naloxone
  4. Xylazine appears to cause necrotic skin wounds at sites of frequent injection
  5. As needed benzodiazepines (e.g. clonazepam) along with adjunctive clonidine, tizanidine, gabapentin, or antipsychotics are commonly deployed in the management of xylazine withdrawal
  6. Weaning patients off full agonist opioids prior to hospital discharge is dangerous because it lowers opioid tolerance and can put them at risk for overdose if they return to illicit opioid use. 

Opioid and Xylazine Withdrawal Show Notes

Xylazine aka “tranq” is a central and peripheral alpha-2 adrenergic agonist similar to clonidine (Ehrman-Dupre, 2022). The main side effect is sedation. A theoretical risk for bradycardia and hypotension exists but does not commonly occur in Dr. D’Orazio’s experience. 

Xylazine is often found as an adulterant of fentanyl possibly because it is relatively cheap and easy to obtain (expert opinion). In Dr. D’Orazio’s experience, many patients want to avoid xylazine.

Recognize xylazine use in the patient with an overdose who does not respond to naloxone (Ball, 2022). Testing is not helpful in the acute setting because it’s a send-out with a slow turnaround time.

It appears to have a toxic effect leading to necrotic wounds in areas of frequent injection (e.g. forearms, legs) that is not seen in other routes of xylazine use. Ehrman-Dupre et al speculate partial alpha-1 agonism with vasoconstriction and ischemia as a mechanism (Ehrman-Dupre, 2022). In Dr. D’Orazio’s experience, the wounds are not particularly painful, but they can become inflamed or superinfected. He notes that wounds can heal once exposure to xylazine stops. Physical or enzymatic debridement of necrotic tissue followed by dressing changes can lead to wound healing over the course of months usually without a need for skin grafting (expert experience). 

Xylazine withdrawal typically manifests within 24 hours and can last 3-5 days or more (expert experience). Anxiety (often severe), restlessness, and dysphoria are common symptoms (Ehrman-Dupre, 2022) without the vital sign abnormalities or seizures seen with alcohol or benzodiazepine withdrawal. 

Kashlak Pearl: Recognize xylazine withdrawal in the patient on an adequate regimen for opioid withdrawal who has residual anxiety/restlessness (expert opinion).

In the ICU, xylazine withdrawal may be dexmedetomidine, or a phenobarbital taper may be used (Ehrman-Dupre, 2022). On the wards, as needed benzodiazepines (e.g. clonazepam 2 mg every 4-6 hours as needed for anxiety) are helpful for many patients (expert opinion). For most patients, Dr. D’Orazio tapers off benzos prior to discharge from the hospital. Don’t miss untreated anxiety disorder and use the opportunity to start long-term therapy! 

Clonidine can be used as an adjunct, but Dr. D’Orazio points out that effective doses are limited by bradycardia and hypotension. Other adjunct medications might include tizanidine, gabapentin (Ehrman-Dupre, 2022), or antipsychotics (for anxiety and insomnia). 

Xylazine use disorder is not a DSM-V diagnosis and is not treated with long-term replacement therapy. That said, some patients might temporarily require treatment of mild ongoing withdrawal symptoms with tizanidine, clonidine, gabapentin, or antipsychotics at hospital discharge (expert opinion). 

Acute Opioid Withdrawal in the Patient not on MOUD

For a full discussion of this topic check out episode #366 Opioid Use Disorder and Acute Pain in the Hospitalized Patient featuring Drs. Carolyn Chan and Shawn Cohen of Curbsiders Addiction Medicine. 

Full agonist opioids are a good starting point for patients not yet on medication for opioid use disorder (MOUD). Dr. D’Orazio prefers scheduled long-acting opioids (e.g. oxycodone ER, or hydromorphone PCA with basal rate) as initial therapy to manage opioid dependence/withdrawal and short-acting full agonists (e.g. hydromorphone IV/PO, oxycodone IR) for acute pain. 

Kashlak Pearl: Weaning patients off full agonist opioids prior to hospital discharge is dangerous because it lowers opioid tolerance and can put them at risk for overdose if they return to illicit opioid use. The period early after hospital discharge is associated with an increased risk of overdose (Lyden, 2023)

Pathways for treatment of opioid withdrawal

  1. Full agonist opioids
  2. Standard or low-dose buprenorphine initiation
  3. Methadone

Dr. D’Orazio lets the patient decide which pathway they’d like to follow based on their situation (e.g. proximity to a methadone clinic, insurance coverage, etc.). 

We should discuss initiating medication for opioid use disorder (MOUD) during hospitalization, but  Dr. D’Orazio prefers to wait until a patient’s withdrawal is adequately treated (usually after 3-5 days) before buprenorphine initiation. 

Dr. D’Orazio cautions that the morphine mg equivalents in a bag of fentanyl differ by region so local guidelines/algorithms/protocols are more practical than a national guideline. 

Precipitated withdrawal occurs when a patient who has full agonist opioids in their system receives a partial opioid agonist (i.e. buprenorphine) causing a sudden relative decrease in opioid receptor activation (Quattlebaum, 2022). 


Relevant links are included in the show notes above


Listeners will diagnose and manage xylazine and opioid withdrawal in the hospitalized patient

Learning objectives

After listening to this episode listeners will…

  1. Recognize features of xylazine toxicity and withdrawal
  2. Treat xylazine withdrawal
  3. Treat opioid use disorder, and acute pain in the hospitalized patient


Dr. D’Orazio reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures. 


Watto MF, D’Orazio J, Okamoto E, Williams PN. “#392 Live! Opioid and Xylazine Withdrawal in the Hospital”. The Curbsiders Internal Medicine Podcast. April 26, 2023.

Episode Credits

Writer and Producer: Matthew Watto MD, FACP Infographic and Cover Art: Matthew Watto MD, FACP Hosts: Matthew Watto MD, FACP; Paul Williams MD, FACP Reviewer: Emi Okamoto MD Showrunners: Matthew Watto MD, FACP; Paul Williams MD, FACP Technical Production: PodPaste Guest: Joseph D’Orazio MD

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The Curbsiders are partnering with VCU Health Continuing Education to offer FREE continuing education credits for physicians and other healthcare professionals. Visit and search for this episode to claim credit.

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