Danbot: Strip excess bold

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Strip excess bold

Danbot: Add MedicationDose entry for atropine

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Add MedicationDose entry for atropine

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 **Warm handoff to addiction services offered (if applicable)
 *'''Lower threshold for admission''' than with opioid-only overdose given prolonged and unpredictable duration of effects
 ==See Also==

Ostermayer: /* Differential Diagnosis */

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Differential Diagnosis

← Older revision		Revision as of 18:47, 8 March 2026
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	*[[Clonidine toxicity]] (very similar presentation)		*[[Clonidine toxicity]] (very similar presentation)
	*[[Organophosphate toxicity]] (miosis, bradycardia, respiratory depression — but typically with copious secretions, SLUDGE)		*[[Organophosphate toxicity]] (miosis, bradycardia, respiratory depression — but typically with copious secretions, SLUDGE)
	*[[Sedative-hypnotic toxicity]]		*[[Sedative/hypnotic toxicity]]
	*[[Beta-blocker toxicity]] (bradycardia, hypotension)		*[[Beta-blocker toxicity]] (bradycardia, hypotension)
	*[[Calcium channel blocker toxicity]] (bradycardia, hypotension)		*[[Calcium channel blocker toxicity]] (bradycardia, hypotension)

Ostermayer: Created page with "==Background== Xylazine (trade names: Rompun, AnaSed, Sedazine) is an '''α₂-adrenergic agonist''' approved '''only for veterinary use''' as a sedative, analgesic, and muscle relaxantXylazine Toxicity. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024. '''Not a controlled substance''' at the federal level (though some states have begun scheduling it); requires only a veterinary prescription to purchase
2026-03-08T18:44:58Z

Created page with "==Background== Xylazine (trade names: Rompun, AnaSed, Sedazine) is an '''α₂-adrenergic agonist''' approved '''only for veterinary use''' as a sedative, analgesic, and muscle relaxant<ref name="StatPearls">Xylazine Toxicity. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024.</ref> '''Not a controlled substance''' at the federal level (though some states have begun scheduling it); requires only a veterinary prescription to purchase<ref name="NEJ..."

New page
==Background==
Xylazine (trade names: Rompun, AnaSed, Sedazine) is an '''α₂-adrenergic agonist''' approved '''only for veterinary use''' as a sedative, analgesic, and muscle relaxant<ref name="StatPearls">Xylazine Toxicity. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024.</ref>
'''Not a controlled substance''' at the federal level (though some states have begun scheduling it); requires only a veterinary prescription to purchase<ref name="NEJM2023">Gupta R, Holtgrave DR, Ashburn MA. Xylazine — Medical and Public Health Imperatives. N Engl J Med. 2023;388(24):2209-2212.</ref>
Increasingly found as an adulterant in the illicit drug supply, most commonly mixed with [[fentanyl]] ("'''tranq dope'''") and in heroin/cocaine mixtures ("speedballs")<ref name="Friedman2022">Friedman J, Montero F, Bourgois P, et al. Xylazine spreads across the US: A growing component of the increasingly synthetic and polysubstance overdose crisis. Drug Alcohol Depend. 2022;233:109380.</ref>
Street names: "tranq," "tranq dope," "sleep cut," "zombie drug," "Anestecia de Caballo" (Puerto Rico)
The White House Office of National Drug Control Policy declared fentanyl mixed with xylazine an '''emerging threat''' to the United States in April 2023<ref name="NEJM2023"/>
'''Not reversed by [[naloxone]]'''; however, naloxone should still be administered in all suspected overdoses because opioid co-ingestion is nearly universal<ref name="NEJM2023"/>
Routes of use: injection (most common), insufflation (snorting), smoking, ingestion
α₂ selectivity of 160:1 over α₁ (compare to [[clonidine]] at 220:1)<ref name="StatPearls"/>
Estimated half-life in humans: 23-50 minutes per FDA; however, clinical effects may last 8-72 hours, likely due to redistribution and co-ingestions<ref name="Sue2024">Sue KL, Hawk K. Clinical considerations for the management of xylazine overdoses and xylazine-related wounds. Addiction. 2024;119(4):606-608.</ref>

===Mechanism of Action===
Activation of '''presynaptic α₂a and α₂c''' receptors in the CNS → decreased norepinephrine and dopamine release → sedation (locus ceruleus) and analgesia (dorsal horn)<ref name="StatPearls"/>
Activation of '''peripheral α₂b''' receptors on vascular smooth muscle → vasoconstriction (may explain skin wound pathology)
At high doses, can activate α₁ and α₂b receptors → paradoxical hypertension (usually transient, followed by sustained hypotension)
Potentiates opioid-induced respiratory depression through an unclear mechanism; animal studies suggest xylazine may blunt compensatory hyperoxic responses to fentanyl<ref name="Sue2024"/>
No activity at opioid receptors — this is why naloxone does not reverse xylazine effects

==Clinical Features==
===Acute Toxicity===
''Clinical presentation is similar to other centrally acting α₂-agonists (e.g. [[clonidine toxicity|clonidine]], [[dexmedetomidine]])''<ref name="ACEP2024">Love JS, Levine M, Aldy K, et al. Opioid overdoses involving xylazine in emergency department patients: a multicenter study. Clin Toxicol. 2023;61(3):173-180.</ref><ref name="StatPearls"/>

'''CNS depression:''' sedation, lethargy, coma
'''Respiratory depression:''' bradypnea, apnea (potentiated by co-ingested opioids)
'''Bradycardia'''
'''Hypotension''' (typically sustained; may be preceded by transient hypertension)
'''Miosis'''
'''Hypothermia'''
Dry mouth
Hyperglycemia
Areflexia
'''Prolonged sedation''' compared to opioid-only overdose — should raise suspicion for xylazine involvement

===Key Distinguishing Feature: Poor Response to Naloxone===
Suspect xylazine when a patient with apparent [[opioid toxicity]] has an '''incomplete or absent response''' to adequate naloxone dosing
Patient may have partial improvement in respiratory depression (due to reversal of co-ingested opioid) but remain significantly sedated and bradycardic

===Xylazine-Associated Skin Wounds===
Severe, necrotic skin ulcerations that are a hallmark of chronic xylazine use<ref name="NEJM2023"/><ref name="McFadden2024">McFadden R, Wallace-Keeshen S, Petrillo Straub K, et al. Xylazine-associated wounds: Clinical experience from a low-barrier wound care clinic in Philadelphia. J Addict Med. 2024;18(1):9-12.</ref>
Can occur at injection sites '''and at distant sites''' on the body
Reported even in individuals who snort or smoke xylazine (do not inject)<ref name="NIDA2024">National Institute on Drug Abuse. Xylazine. Updated September 18, 2024.</ref>
Wounds may progress to deep necrotic ulcers with eschar; can involve underlying tendons, bone
Pathophysiology is poorly understood; likely involves peripheral vasoconstriction, obliterative vascular injury from repeated injection, and possible locally toxic extravasation<ref name="Sue2024"/>
Wounds are '''not intrinsically infected''' but are at risk for superinfection
If untreated, may require surgical debridement or, rarely, amputation
Ask about skin wounds in patients presenting with opioid overdose — this may be the first clue to xylazine exposure

===Xylazine Withdrawal===
Patients with chronic use may develop physiological dependence<ref name="NEJM2023"/>
Withdrawal symptoms can include: anxiety, agitation, irritability, diaphoresis, insomnia
Limited data on management; some centers use [[clonidine]], [[lofexidine]], or [[dexmedetomidine]] infusions (ICU setting) to treat withdrawal<ref name="NEJM2023"/><ref>Ehrman-Dupre R, et al. Management of Xylazine Withdrawal in a Hospitalized Patient: A Case Report. J Addict Med. 2022;16(5).</ref>
Tapering α₂-agonists over 5-7 days may be appropriate; evidence is limited

==Differential Diagnosis==
[[Opioid toxicity]] (most common co-ingestion)
[[Clonidine toxicity]] (very similar presentation)
[[Organophosphate toxicity]] (miosis, bradycardia, respiratory depression — but typically with copious secretions, SLUDGE)
[[Sedative-hypnotic toxicity]]
[[Beta-blocker toxicity]] (bradycardia, hypotension)
[[Calcium channel blocker toxicity]] (bradycardia, hypotension)
[[Hypothermia]]
[[Hypoglycemia]]
Pontine hemorrhage ([[CVA]] — miosis, coma)
[[Carbon monoxide toxicity]]

{{Sedatve/hypnotic toxicity types}}

==Evaluation==
===Workup===
'''Fingerstick glucose''' (rule out [[hypoglycemia]]; xylazine itself can cause hyperglycemia)
'''[[ECG]]''' — assess for [[bradycardia]], heart blocks, [[QT prolongation]] (if [[methadone]] co-ingestion suspected)
'''Cardiac monitoring''' — continuous telemetry
'''Temperature''' — assess for [[hypothermia]]
'''[[CXR]]''' — if concern for aspiration or [[noncardiogenic pulmonary edema]]
'''[[Acetaminophen]] level, [[salicylate]] level''' — standard toxicology screen for co-ingestion
'''[[VBG]] or [[ABG]]''' — if significant respiratory depression
'''[[BMP]]''' — glucose, renal function, electrolytes
'''[[CK]]''' — if prolonged immobilization (concern for [[rhabdomyolysis]])
'''[[Lactate]]''' — if concern for end-organ hypoperfusion from prolonged hypotension
'''[[Utox]]''' (standard urine drug screen) — will '''not''' detect xylazine or fentanyl; useful to identify other co-ingestions
'''Skin exam''' — inspect for necrotic ulcerations (may be present on extremities even remote from injection sites)

===Diagnosis===
'''Primarily clinical:''' suspect xylazine when a patient presents with opioid-like toxidrome (miosis, respiratory depression, bradycardia) and has a '''poor or incomplete response to naloxone'''
Standard urine immunoassay drug screens do '''not''' detect xylazine<ref name="StatPearls"/>
Newer immunoassay-based xylazine tests are being developed but are not widely available as point-of-care tests
Definitive detection requires gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-tandem mass spectrometry (LC-MS/MS); turnaround time is days, so this does '''not''' guide acute ED management<ref name="StatPearls"/>
'''Xylazine test strips''' (for checking drug supply) are available through some harm reduction programs; these test the drug product, not the patient

==Management==
''There is '''no specific antidote''' for xylazine in humans. Management is '''supportive care'''.''<ref name="NEJM2023"/><ref name="StatPearls"/>

===Airway and Breathing===
'''Airway protection''' and '''ventilatory support''' are the '''top priority'''
Provide '''BVM ventilation''' and supplemental O₂ as needed
'''Administer [[naloxone]]''' — will not reverse xylazine effects but will treat the nearly universal opioid co-ingestion<ref name="NEJM2023"/>
Use standard naloxone dosing (see [[Opioid toxicity]])
Expect a partial or blunted response compared to opioid-only overdoses
[[Intubation]] if patient cannot protect airway or has persistent apnea despite naloxone
Prolonged respiratory support may be required (effects can last hours)

===Cardiovascular===
'''[[Bradycardia]]:'''
'''[[Atropine]]''' 0.5-1 mg IV; may repeat q3-5 min (max 3 mg)
Transcutaneous or transvenous '''pacing''' if refractory to atropine
'''[[Hypotension]]:'''
'''IV crystalloid''' bolus (e.g. 500-1000 mL [[normal saline]] or [[Lactated Ringer's]])
'''[[Norepinephrine]]''' infusion if refractory to fluids (preferred given α-agonist mechanism of injury and concurrent vasodilation)
Transient hypertension may occur early and generally does not require treatment unless severe/symptomatic

===Hypothermia===
'''Active rewarming''' measures as indicated (see [[Hypothermia]])

===Hyperglycemia===
Usually self-limited; monitor glucose
Treat with [[insulin]] only if severely elevated with clinical consequence

===Skin Wounds===
Perform thorough skin exam on all patients with suspected xylazine exposure
'''Wound care:''' keep wounds moist, clean, and covered; chemical or enzymatic debridement of eschar often preferred over surgical debridement by patients<ref name="Sue2024"/><ref name="McFadden2024"/>
Assess for signs of superinfection (purulence, spreading erythema, cellulitis) and treat with antibiotics if indicated
Consult wound care or surgery for deep or extensive wounds
Connecting patient to outpatient wound care follow-up is critical
Initiating or increasing [[buprenorphine]] or [[methadone]] may help reduce injection frequency and promote wound healing<ref name="Sue2024"/>

===Harm Reduction at Discharge===
'''[[Naloxone]] distribution:''' Provide or direct to OTC Narcan (4 mg nasal spray); naloxone will not reverse xylazine but will address opioid component of polysubstance overdose
'''Xylazine test strips''' (where available): enable users to test drug supply
'''Fentanyl test strips'''
'''Education:''' counsel that xylazine-adulterated opioids may cause prolonged sedation and that naloxone alone may not fully reverse overdose
'''Never Use Alone''' hotline: encourage patients to have someone present when using
'''[[Buprenorphine]] initiation:''' offer ED-initiated buprenorphine for patients with [[opioid use disorder]] (see [[Opioid toxicity]])

===Investigational Reversal Agents===
'''Atipamezole:''' potent α₂-antagonist used as a veterinary reversal agent for xylazine; was briefly approved for human use (1970-2017) but is '''no longer FDA-approved''' for humans; active clinical investigation is underway<ref name="StatPearls"/>
'''Yohimbine:''' natural α₂-antagonist; has reversed xylazine effects in animal models; '''not approved''' for this indication in humans
'''Tolazoline:''' α₂-antagonist used in veterinary medicine; '''not approved''' for this use in humans
None of these agents should be administered outside of a clinical trial or toxicology consultation

==Disposition==
'''Observation:''' Prolonged observation is warranted; effects of xylazine may last '''8-72 hours''', significantly longer than most opioids<ref name="StatPearls"/>
'''Admit''' if:
Persistent respiratory depression requiring supplemental O₂ or ventilatory support
Hemodynamically unstable (refractory bradycardia, hypotension requiring vasopressors)
Hypothermia requiring active rewarming
Significant skin wounds requiring inpatient wound care or surgical consultation
**Concern for ongoing withdrawal requiring α₂-agonist taper
*'''Consider discharge''' only if:
Hemodynamically stable and asymptomatic for a minimum of '''4-6 hours''' after last intervention
Ambulatory, GCS 15, RR >12, HR >50, SpO₂ >92% on room air
Skin wounds (if present) have been assessed with outpatient wound care follow-up arranged
Naloxone and harm reduction supplies provided
**Warm handoff to addiction services offered (if applicable)
'''Lower threshold for admission''' than with opioid-only overdose given prolonged and unpredictable duration of effects

==See Also==
[[Opioid toxicity]]
[[Clonidine toxicity]]
[[Naloxone]]
[[Opioid withdrawal]]
[[Fentanyl]]
[[Buprenorphine]]

==External Links==
[https://nida.nih.gov/research-topics/xylazine NIDA - Xylazine Overview]
[https://www.cdc.gov/overdose-prevention/media/pdfs/2024/07/Xylazine-Clinical-Management-and-Harm-Reduction.pdf CDC - Xylazine Clinical Management and Harm Reduction Fact Sheet (2024)]
[https://www.nejm.org/doi/full/10.1056/NEJMp2303120 NEJM - Xylazine: Medical and Public Health Imperatives (2023)]
*[https://www.acep.org/toxicology/newsroom/may-2024/xylazine-a-confounding-adulterant ACEP Toxicology Section - Xylazine: A Confounding Adulterant (2024)]

==References==
{{reflist|2}}

[[Category:Toxicology]]

Xylazine - Revision history

Danbot: Strip excess bold

Danbot: Add MedicationDose entry for atropine

Ostermayer: /* Differential Diagnosis */