Field Brief: Xylazine & Emerging Non-Opioid Street Drugs

Introduction

Xylazine – also known by street names like “tranq” or “tranq dope” – is a veterinary sedative that has rapidly infiltrated the illicit drug supply in recent years. Unlike opioids, xylazine is not intended for human use, yet it’s being combined with fentanyl and other drugs, causing unprecedented challenges for emergency medical services (EMS).

This report provides a comprehensive overview of xylazine and similar emerging non-opioid drugs (e.g. medetomidine, nitazenes), tailored for EMS instructors training EMTs, AEMTs, and Paramedics. We cover xylazine’s history, pharmacology (in digestible terms), street usage, health effects, and the scope of the problem. We then highlight EMS-specific concerns – recognizing xylazine in the field, why naloxone often fails, managing “tranq” overdoses, treating the infamous necrotic wounds, provider safety, and protocol adjustments. We also introduce other new adulterants like nitazene opioids and medetomidine (“Dex”), discussing their pharmacology and field treatment. Finally, we suggest evidence-based best practices (from CDC, NIDA, SAMHSA, etc.), share case studies/anecdotes for teaching, list must-know facts for providers, and explain how xylazine is sourced in the illicit market. Our goal is to equip EMS educators with current, credible information and actionable takeaways about these emerging drug threats.

1. History of Xylazine: From Vet Tranquilizer to Street “Tranq”

Veterinary Origins: Xylazine was first introduced in the 1960s as a sedative, analgesic, and muscle relaxant for veterinary use. Commonly sold under brand names like Rompun or Anased, it became popular for sedating large animals (e.g. horses, cattle) during procedures. Because of its potent α2-adrenergic agonist effect (similar to drugs like clonidine and dexmedetomidine), xylazine induces deep sedation and pain relief in animals. Importantly, it was never approved for human use due to dangerous side effects like severe hypotension, bradycardia, and hyperglycemia. Xylazine remains a prescription-only veterinary drug in the U.S., unscheduled at the federal level (not a controlled substance) despite recent legal scrutiny.

Early Illicit Abuse: Xylazine misuse in humans was first reported in Puerto Rico in the early 2000s. On the island it was nicknamed “Anestesia de Caballo” (“horse anesthetic”) and used as an additive in injectable heroin, contributing to a wave of soft-tissue infections and overdose. For about a decade, xylazine abuse remained a localized phenomenon (notably in PR’s drug scene), with sporadic reports elsewhere. However, by the mid-2010s, xylazine began appearing in the mainland U.S. illicit opioid supply. The first detections in the continental U.S. occurred around 2010–2015 but were infrequent. After 2015, its presence started to rise, particularly in the Northeast. One analysis noted xylazine in <2% of overdose cases from 2010–2015, but by 2019 it was present in 31% of heroin/fentanyl overdose deaths (in one region). Law enforcement and medical examiners in states like Pennsylvania, Connecticut, and New York began sounding alarms about this emerging adulterant around 2019–2020.

Rapid Spread (2020s): In the past five years, xylazine has exploded across the U.S. drug supply. It was first identified in 48 of 50 states by late 2022. The prevalence of xylazine in opioid overdose deaths climbed dramatically – increasing 20-fold between 2015 and 2020 in some areas. By 2021–2022, xylazine was detected in an estimated 5–11% of opioid overdose fatalities nationally. For example, provisional CDC data showed xylazine present in 5.6% of opioid-involved overdose deaths in 2022 (up from 1.8% in 2019). Certain hotspots saw even higher rates: Philadelphia reported xylazine in over 25–30% of fatal opioid ODs by 2021 and Connecticut recorded xylazine in 11.4% of OD deaths in early 2020. Initially concentrated in the Northeast (Pennsylvania, New York, New Jersey, New England), the xylazine problem now spans urban and rural communities nationwide. Even rural states like West Virginia noted a >6-fold increase in xylazine-related deaths in recent years. By 2023, xylazine had become so prevalent alongside fentanyl that the White House Office of National Drug Control Policy officially designated fentanyl mixed with xylazine as an “emerging threat” to the nation. Some states (e.g. Florida in 2016, Pennsylvania in 2023) moved to schedule xylazine as a controlled substance due to rising abuse, although its legitimate veterinary use complicates outright bans.

Key Takeaways:: Xylazine’s evolution from a niche veterinary tranquilizer to a widespread street drug took roughly two decades. It started with isolated misuse (Puerto Rico) and minor appearances in U.S. drug markets, then surged around 2019 onward in tandem with the fentanyl epidemic. Lack of legal controls and cheap availability (discussed later) accelerated its spread. Today, “tranq dope” is a fixture in many opioid-using communities, representing a new chapter in the overdose crisis that EMS providers must confront.

2. Pharmacology of Xylazine: How It Works (and Harms)

Mechanism of Action: Pharmacologically, xylazine is a potent α2-adrenergic receptor agonist in the central nervous system. In simpler terms, it works much like clonidine or dexmedetomidine, suppressing the release of excitatory neurotransmitters (norepinephrine and dopamine) in the brain and spinal cord. This leads to a depressed CNS state – sedation, analgesia (pain relief), muscle relaxation, and slowed autonomic functions. Xylazine’s chemical structure is analogous to clonidine (an antihypertensive sedative) and even shares similarities with tricyclic antidepressants and phenothiazines.

In veterinary practice, small doses produce reliable sedation within minutes, lasting 1–2 hours, with analgesic effects for 15–30 minutes. The drug also causes peripheral α1 receptor stimulation initially, which can transiently elevate blood pressure before central sedation leads to hypotension.

Clinical Effects in Humans: In humans, xylazine has opioid-like effects in some respects, but through different pathways. Key physiological effects of xylazine include:

Profound Sedation: Patients appear very drowsy, lethargic, or unresponsive (“nod out”). Xylazine “slows down the brain,” often inducing a semi-conscious, stuporous state. This heavy sedation can last far longer than opioid highs – reports range from a couple of hours up to 8 or even 24–72 hours of depressed consciousness in extreme cases. Users may literally be immobilized for hours, which poses risks discussed later.

Respiratory Depression: Breathing becomes slow and shallow. Xylazine by itself can depress respiratory drive, and when combined with opioids, it potentiates respiratory depression synergistically. EMS might find patients with dangerously low respiratory rates or apnea.

Bradycardia & Hypotension: Heart rate and blood pressure drop significantly. As an α2 agonist, xylazine triggers vagal effects – slow pulse and vasodilation. Patients often present with bradycardia and low blood pressure (after any initial spike) This can progress to hemodynamic instability in an overdose. Xylazine overdose closely mimics clonidine overdose, showing miosis (pinpoint pupils), bradycardia, hypotension, hypothermia, and coma.

Analgesia: Xylazine provides pain relief, which may be one reason dealers and users find it desirable to enhance opioids. However, at high doses, analgesia may be overshadowed by deep sedation and anesthetic effects.

Hyperglycemia: A lesser-known pharmacologic effect – xylazine causes a transient increase in blood sugar levels. It reduces insulin release via α2 receptors, leading to elevated serum glucose (observed in both animals and human cases). EMS providers might notice unexpectedly high finger-stick glucose in an unresponsive xylazine patient. This hyperglycemia is usually temporary, but it’s a reminder that xylazine can affect multiple organ systems (endocrine, etc.). Other autonomic effects noted in veterinary literature include increased urination (diuretic effect) and reduced GI motility.

Other Effects: Xylazine causes central nervous system depression to the point of decreased reflexes. Gag reflex may be diminished, raising aspiration risk. It also induces muscle relaxation and loss of coordination – users can slump in odd positions. Notably, chronic xylazine use is linked to skin ulcers (discussed separately) and, per some reports, physical dependence with a withdrawal syndrome (though typically milder than opioid withdrawal).

Why Is Xylazine Used as an Adulterant? 

Despite its dangers, traffickers and some users exploit certain properties of xylazine:

Prolonging the High: Fentanyl’s euphoric effects are intense but short-lived (often 1–2 hours or less). Xylazine, being a long-acting sedative, can extend the overall drug effect duration. Street lore suggests xylazine can stretch a fentanyl high from ~30 minutes to several hours (even up to 6–8+ hours) Essentially, it “downers out” the user for a long time, which some dependent individuals see as getting more bang for their buck. Users seeking a longer period of intoxication or relief from withdrawal symptoms may appreciate this extended sedation.

Enhanced Sedation/Potentiation: Xylazine’s sedative and analgesic actions potentiate opioid effects, making a drug batch feel stronger. This can increase the perceived potency of heroin/fentanyl, even if actual opioid content is lower. Sadly, this also increases overdose risk (more profound CNS depression).

Cheap Filler: Xylazine is inexpensive and easy to obtain. It is not controlled federally and could be bought in bulk from chemical suppliers. In fact, suppliers (often in China) sell xylazine powder online for as low as $6–$20 per kilogram – an incredibly cheap cutting agent. By adding xylazine, dealers can bulk up product weight and reduce the amount of pricey fentanyl/heroin needed, boosting profit. The psychoactive “kick” from xylazine helps mask dilution, whereas inert fillers would be obvious to users.

User Demand: While many users unknowingly consume xylazine, a subset actively seek “tranq dope.” They may crave the heavy sedative effect or longer-lasting high, especially those with co-occurring anxiety or insomnia. Some anecdotal reports say xylazine’s effect can “take the edge off” the jittery rush of stimulants or the intense nod of fentanyl. However, others avoid it, complaining it reduces euphoria or causes terrible side effects. It’s a mixed bag – some opioid users intentionally look for xylazine-laced product, whereas others fear it for the ulcers and stupor it brings.

Key Takeaways: Xylazine pharmacologically sedates and depresses body systems in a way that both complements and complicates opioid intoxication. For EMS, it’s crucial to recognize that a patient deeply unresponsive with slow respirations and bradycardia might not be a pure opioid overdose – a non-opioid sedative like xylazine could be contributing to the clinical picture, which changes the acute management strategy.

3. Street Names, Combinations, and Typical Use Patterns

On the street, xylazine has gained infamy under several slang names. In the U.S., the most common nicknames are “Tranq”, “Tranq Dope”, and “Sleep Cut.” These refer to xylazine typically when mixed into opioids (hence tranq dope for tranquilizer-laced dope). The term “sleep cut” highlights its sedative potency – a cut that “puts you to sleep.” In Puerto Rico, as noted, it’s long been called “Anestesia de Caballo” (horse anesthetic).

Some users and dealers also simply call it “zombie drug” or “zombie tranq” due to the stupor and the rotting skin wounds it can cause (media headlines have popularized the “zombie” moniker, although it’s more sensational than scientific). Medically, one might hear it referenced as xyla or by its pharmaceutical name, but on scene EMS will more likely hear laypersons say someone took “tranq” or “booted up some tranq dope.”

Common Drug Combinations: Xylazine is rarely used entirely on its own by humans; it is almost always encountered as an adulterant in other illicit drugs. The opioid supply (fentanyl and heroin) is where xylazine is most prevalent. Over 98% of xylazine-positive overdose deaths also involve fentanyl or heroin. Thus “fentanyl mixed with xylazine” – often called “Fenyla” in some circles – is a common combo. Another frequent combo is a “speedball” type mixture: heroin/fentanyl (downer), cocaine (upper), and xylazine thrown in. Xylazine has indeed been found as an adulterant in mixtures of fentanyl and cocaine or methamphetamine. In one analysis of xylazine-related deaths in Connecticut, 85.6% of cases had other substances present, including cocaine (34%), heroin (30%), benzodiazepines (26%), alcohol (22%), and gabapentin (12%). This reflects polysubstance use patterns: people may co-use stimulants or depressants, or the supply itself is a messy poly-drug mix.

Xylazine in counterfeit pills is also a new concern – the DEA reported about 7% of fake fentanyl pills it seized in 2022 contained xylazine. So a patient overdosing on what they thought was an “oxy” tablet could also have xylazine on board. Less commonly, xylazine has been detected in illicit benzodiazepine powders or pills, and in some cannabinoid or synthetic drug samples, but these are very limited reports.

Routes of Administration: The majority of people exposed to xylazine inject it, because it’s usually in injectable opioid mixtures. In one study of overdose scenes, ~40% had evidence of IV use (needles) when xylazine was involved. However, xylazine can be snorted or smoked as well, if it’s present in powdered or rock form drugs (like heroin/fentanyl powder, or crack laced with xylazine). Around 15% of cases in Connecticut involved snorting and 14% smoking. It’s also possible to ingest it orally, and there are rare cases of intentional ingestion, but this is a minor route (~4%). For EMS, this means patients can present with xylazine toxicity whether they injected, snorted, or smoked their drugs – any opioid/street drug overdose could involve xylazine. The onset via IV is rapid (seconds to minutes to knock someone out), whereas intranasal or inhalation might be a bit slower to hit.

Typical Cost and Availability: From the trafficker’s perspective, xylazine is dirt cheap and accessible. As mentioned, bulk xylazine can be bought online without vet credentials in powder form often sourced from China (since it’s not federally scheduled) At about $10 per kilogram a dealer can cut a huge quantity of product.

On the street, users typically aren’t buying “pure xylazine” bags – it’s just mixed in. But in some areas like Philadelphia’s Kensington neighborhood, reports indicate that some bags of “dope” might be predominantly xylazine and filler with little fentanyl, sold under opioid branding. A user may pay the usual price (~$5-10 per bag in some cities for a hit of fentanyl dope) not realizing half of it is xylazine. There isn’t clear data on xylazine-specific pricing because it’s an additive; however, the low wholesale cost is a major reason it’s rampant as an adulterant.

Key Takeaways: Xylazine is usually hidden in other street drugs – primarily opioids – rather than sold outright. It goes by innocuous street terms like tranq, and its use patterns (injection, etc.) mirror those of the drugs it laces. The poly-drug nature also means EMS must consider that a xylazine patient could have multiple substances on board (opioids, stimulants, benzos, etc.), each requiring attention.

4. Scope of the Problem: Prevalence, Trends, and Public Health Concerns

Xylazine’s rise has introduced a host of new public health challenges on top of the ongoing opioid epidemic. Understanding the scope – how widespread and severe the xylazine problem is – will help EMS providers appreciate why special training and protocols are needed.

Prevalence and Geography: Xylazine has swiftly gone from regional oddity to national threat. By late 2022, DEA seizures showed xylazine in fentanyl products in 48 states. In 2022, approximately 23% of powdered fentanyl samples and 7% of fentanyl pills analyzed by DEA labs contained xylazine. These figures indicate that nearly 1 in 4 batches of illicit fentanyl powder is adulterated with xylazine – an astonishing penetration into the drug supply. The problem initially was most dire in the U.S. Northeast (Philadelphia is often cited as “ground zero” for tranq), but states across the Midwest, South, and West Coast are now reporting xylazine in overdoses. For instance, Illinois recorded xylazine in more than 200 overdose death toxicology reports in 2022 (up from 45 cases in 2020). Pennsylvania’s preliminary data for 2022 found xylazine contributed to over 600 deaths across 38 counties. Even California and other western states, which were initially spared, are detecting tranq in their drug supplies.

Internationally, xylazine abuse has been documented in Canada (notably in Ontario’s opioid supply) and was reported for the first time in a European overdose death in 2022. Puerto Rico continues to have entrenched xylazine use as well. While our focus is U.S., it’s worth noting the spread is not confined to one country.

Trends Over Time: All data points to rapid growth in xylazine involvement. The CDC reported that nationally, xylazine was present in 1.8% of all overdose deaths in 2019, but in 2022 it was found in 5.6% of opioid-related deaths. That’s a threefold increase in just a few years. In places like Philadelphia, the proportion of opioid deaths with xylazine jumped from 2% in 2010 to 31% in 2919, reflecting the dramatic local surge. Another study found xylazine-positive OD deaths in Connecticut nearly doubled from ~6% in 2019 to 11.4% in the first half of 2020. The Kensington area of Philly saw xylazine in virtually all dope by 2022. However, 2024–2025 developments suggest an evolving trend: in Philadelphia, xylazine’s dominance might be waning in favor of a new sedative (medetomidine – discussed later), possibly due to law enforcement crackdowns on xylazine supply. But as of now, xylazine still remains widespread across the country. The White House in July 2023, recognizing these trends, launched a National Response Plan specifically targeting “fentanyl mixed with xylazine”.

Demographics: Who is affected by xylazine? Largely, it’s the same population affected by opioid addiction: adults in their 20s to 50s, often with a history of IV drug use. Data from Connecticut’s 2019–20 xylazine overdose deaths showed 81% male, 74% non-Hispanic white. The most common age group was 25–34 years old (28%), closely followed by 35–44 (27%). Notably, a sizeable 23% were age 55 or older. suggesting older individuals with long-term opioid use are also at risk. Tennessee’s 2020–21 nitazene (a synthetic opioid) deaths had an average age around 41., indicating a similar demographic for emerging drugs – typically adult opioid users, typically not teenagers or people new to drug use.

Xylazine doesn’t seem to be drawing in completely new demographics; rather, it’s worsening outcomes for existing opioid-using populations. Socioeconomically, many of those impacted are experiencing homelessness or unstable housing, especially in urban centers like Philly, which exacerbates wound care issues (lack of hygiene, etc.). However, rural opioid users are not immune – xylazine has permeated rural drug markets too.

Public Health Concerns: The rise of xylazine brings several serious concerns:

Increased Overdose Fatalities: The combination of xylazine with fentanyl is making the deadliest drug (fentanyl) even deadlier. Xylazine’s sedative effect synergizes with opioids to further depress breathing and consciousness. Critically, naloxone does not reverse xylazine (more on this in EMS section), meaning standard overdose reversal may fail if xylazine is present. This can lead to more deaths even when bystanders or first responders administer Narcan. The CDC estimated over 107,000 overdose deaths occurred in the year ending Aug 2022, and xylazine likely contributed to a growing fraction of these. Communities are seeing overdose patients who remain unresponsive after naloxone – a frightening scenario for both families and EMS.

Severe Soft Tissue Wounds: Xylazine causes horrific skin lesions, a unique public health problem distinct from other drugs. People who inject tranq dope can develop ulcers, abscesses, and necrotic (rotting) tissue at injection sites – or even in areas where they didn’t inject.

These “tranq wounds” often start as small, odd skin sores but can rapidly progress to large necrotic ulcers requiring surgical debridement or even amputation. Unlike typical injection abscesses which usually localize to the needle site, xylazine-associated wounds have been reported on legs, arms, and other body parts regardless of injection location. Some occur in people who don’t inject but snort or smoke – possibly due to xylazine’s vasoconstrictive effects causing skin ischemia systemically. The exact mechanism isn’t fully understood, but local vasospasm and compromised blood flow appear to play a role, along with adulterants and poor wound healing in sedated users. From a public health perspective, these wounds have led to an increase in hospitalizations, antibiotics usage, and burden on wound care centers. They also pose a risk of severe infections (cellulitis, sepsis, osteomyelitis). Essentially, xylazine is causing a wave of complex, chronic wound cases in an already vulnerable population.

Emergence of Dependence & Withdrawal: Chronic xylazine use may lead to physical dependence. People using tranq heavily over weeks can experience a withdrawal syndrome when it’s absent. Xylazine withdrawal symptoms reported are anxiety, irritability, restlessness, and possibly rebound hypertension/tachycardia (similar to clonidine withdrawal).

Fortunately, xylazine’s withdrawal in humans has been generally described as milder than opioid withdrawal – often just anxiety and insomnia without major vital sign instability. However, as people become accustomed to tranq, they may continue seeking it to avoid discomfort. This complicates treatment: some opioid treatment programs now have to manage xylazine withdrawal in addition to opioid withdrawal. (Notably, medetomidine’s withdrawal is even worse – covered later.) The presence of another addictive sedative in the drug supply adds a new layer of dependency to address.

Healthcare System Strain: Hospitals in heavily affected areas have reported surges in patients with prolonged sedation and intractable wounds. These cases often require longer ICU stays (for unresponsive overdose patients who can’t be discharged quickly) and lengthy hospitalizations for wound infections. For example, one xylazine overdose patient in a case study required a 14-day hospital stay including ICU intubation and multiple surgical debridement of wounds. This is far more resource-intensive than a typical opioid OD reversal and discharge. EMS systems also face increased call volumes for recurrent overdoses in the same patients and more “man down” calls for individuals sedated in public for hours. The public health system is grappling with how to provide wound care to people who often remain actively using and housing-insecure.

Vulnerability and Social Risks: Xylazine’s immobilizing effect puts users at risk of injury and victimization. Because tranq can knock someone out for hours, people have woken up with unattended fractures or having laid in one position so long they developed pressure ulcers or compartment syndrome. There are reports of users being robbed or sexually assaulted while sedated on xylazine. This adds an extra humanitarian concern beyond the pharmacological effects. Outreach workers note that people “checking out” on tranq need someone to watch over them, otherwise they’re extremely vulnerable on the streets.

Key Takeaways: The scope of xylazine’s impact is broad: increasing overdose deaths, devastating flesh wounds, complicated withdrawal/treatment needs, and new safety risks for users. For EMS and public health officials alike, xylazine demands a specialized response to reduce these harms. Next, we’ll zero in on what EMS providers specifically need to know and do when encountering xylazine in the field.

5. EMS-Specific Concerns and Field Management

Recognizing Xylazine in the Field: Signs & Symptoms

For EMS crews, a xylazine-intoxicated patient will often look like an opioid overdose, with some nuances.

Key clinical signs EMS might observe include:

Profound CNS Depression: The patient may be unconscious or minimally responsive. They often present in a limp, slumped posture (sometimes nicknamed the “zombie” stance if still semi-upright, due to muscle relaxation). Expect very difficult arousal – sternal rub or shouting yields little to no response beyond maybe groans.

Respiratory Depression: Respirations are slow and shallow. Count respirations; xylazine overdoses often have RR well under 12/min, sometimes apneic. Oxygen saturation may be low due to hypoventilation (e.g., SpO₂ in 80s). First responders have noted that giving rescue breaths often significantly helps these patients (because xylazine doesn’t paralyze breathing completely, but induces dangerous hypoventilation).

Bradycardia: Check the pulse – xylazine usually causes a slow heart rate (often <60 bpm). This is a distinguishing feature; pure opioid ODs can have bradycardia too, but xylazine’s α2 effects reliably drop the heart rate. In one case, however, a patient had an initial heart rate of 128 with BP 180/96 despite being comatose – likely due to a brief adrenergic surge or possible co-stimulant use. But typically, expect bradycardia followed by hypotension as the prevailing trend.

Hypotension (sometimes preceded by hypertension): It’s possible to see an elevated blood pressure early on (xylazine can cause an initial peripheral vasoconstriction). However, this often transitions to significant hypotension as sedation deepens. Many xylazine OD patients will have low systolic BP, e.g., 70–90 mmHg, especially if also hypoxic or acidotic. For EMS, persistent hypotension is a red flag that the overdose is not a simple opioid (fentanyl alone usually doesn’t cause such severe hypotension unless in extreme OD or late stage).

Miosis: Pupils are typically pinpoint (miotic), just like an opioid OD. Xylazine and clonidine analogs cause miosis as well. So the presence of pinpoint pupils doesn’t tell you it’s not xylazine – in fact, it often is present with fentanyl so pupils will still be tiny. Of note, if other drugs like stimulants are present, pupils could be variable, but the classic tranq dope presentation is pinpoint pupils with deep sedation.

Snoring or Gurgling Airway: Because of relaxed muscle tone, these patients often have partial airway obstruction – you might hear snoring respirations or gurgling if vomitus is present. The gag reflex may be blunted, increasing risk of aspiration. Check for cyanosis or pallor (xylazine’s vasoconstriction and poor perfusion can cause a pale or bluish appearance, plus the hypoxia).

Skin Wounds: One hallmark that can tip off EMS to xylazine use is the presence of unusual skin ulcers or abscesses, often on the extremities. If the patient’s arms or legs have visible, open wounds with blackened eschar or necrotic tissue, consider xylazine.

These “tranq burns” are often described as deep, necrotic ulcerations, sometimes with surrounding cellulitis. They might be malodorous and obviously infected. Patients might also have bandaged arms/legs from prior wounds or scars from healed ulcers. While not every xylazine user has wounds (especially early on), a significant number do, and it’s a distinguishing clue – typical heroin or fentanyl use alone doesn’t cause such severe skin lesions in atypical locations. Always expose and check high-risk sites (common: legs, feet, arms) if the situation allows, to not miss these wounds.

Unresponsiveness to Naloxone: Perhaps the most practical sign for EMS is if naloxone is given with little or no effect on mental status or breathing. Many xylazine cases come to light after bystanders or police administer Narcan thinking it’s an opioid overdose – when the patient fails to wake up after 2, 4, or even 6+ mg of naloxone, xylazine is a likely culprit. We will discuss this in detail next, but from a diagnostic standpoint, “naloxone-refractory overdose” strongly suggests a non-opioid sedative or polysubstance scenario (xylazine, benzos, etc.). As one medical director succinctly put it: poor or no response to naloxone is a hallmark of xylazine presence.

Other findings: Xylazine causes muscle relaxation, so patients may be very floppy, with low muscle tone. They might have signs of chronic use like track marks, but so do opioid users in general. Some xylazine users report “memory gaps” or confusion upon awakening. On ECG, aside from bradycardia, there aren’t specific arrhythmias tied to xylazine (it’s not known for QT prolongation like some sedatives). Temperature might be low; xylazine can induce hypothermia (due to CNS depression and vasodilation), so check if they feel cool.

Key Takeaways: In short, EMS should suspect xylazine in any overdose patient who remains deeply unconscious with slow breathing despite naloxone, especially if accompanied by bradycardia, hypotension, and unusual wounds. It will often be indistinguishable from a classic opioid OD at first glance, so maintaining a high index of suspicion is key.

Why Naloxone Won’t Work (and Why You Should Still Give It)

Naloxone (Narcan) is the opioid overdose antidote, but xylazine is not an opioid. It does not bind to opioid receptors at all, so naloxone has no direct effect on xylazine’s actions. This is critical for EMS to understand: giving more Narcan will not magically reverse a xylazine-induced coma. Paramedics have seen this first-hand – patients unresponsive after multiple naloxone doses until proper supportive care is given.

However, mixed overdoses (xylazine + fentanyl) are the norm, not pure xylazine. Thus, standard practice is to administer naloxone in any suspected opioid overdose (including those likely involving xylazine). Naloxone will address the fentanyl/heroin part of the overdose, reversing opioid-caused respiratory depression. It just won’t touch the xylazine-caused sedation. Experts universally recommend continuing to use naloxone in the field for presumed opioid ODs even if xylazine is suspected.

The opioid component still needs reversal – in fact, unmasking the xylazine is beneficial. Once you give naloxone, the patient may start breathing a bit better if opioids were suppressing respirations. What remains is the xylazine effect: the patient could still be sedated and hypotensive even after Narcan, which tells you “Okay, it’s likely tranq (or benzos) causing the residual CNS depression.”

One caution: Because xylazine can cause very long-lasting sedation, the effect of naloxone (which lasts 30-90 minutes) may wear off while xylazine is still active. A patient might re-sedate or re-respiratory-depress once naloxone wears off if any opioid is still present in their system and the xylazine is keeping them out (this is more of a hospital monitoring issue, but EMS should be aware that just because you got a minimal response after Narcan doesn’t mean they’re out of the woods).

It’s worth noting that there is no specific antagonist for xylazine approved in humans. In veterinary medicine, drugs like yohimbine and atipamezole can reverse xylazine’s effects by blocking α2 receptors. However, these are not used in humans (atipamezole isn’t FDA-approved for humans and giving it could cause dangerous blood pressure spikes or arrhythmias). So, unlike an opioid overdose where we push Narcan, or a benzodiazepine OD where (rarely) flumazenil might be considered, for xylazine there is no reversal agent EMS or hospitals can use. We rely entirely on supportive care (airway, breathing, circulation support) to get the patient through it.

Some EMS protocols have been updated to emphasize “don’t waste time with excessive naloxone” if the patient isn’t responding. One case report describes bystanders giving 6 mg of Narcan with zero change in the patient’s condition (because it was tranq dope). In such cases, after the initial 1–2 doses of naloxone, providers should shift focus to airway management and other interventions rather than escalating naloxone to enormous doses. High-dose naloxone won’t hurt the patient (if no opioids, it’s just inert), but it delays the real treatment needed (ventilation, fluids, etc.). The key is to recognize when naloxone isn’t working and promptly pivot to supportive measures.

Key Takeaways: Naloxone is still your first step in any suspected opioid overdose – xylazine often accompanies opioids so you must treat the opioid part. But do not be surprised when it doesn’t fully revive the patient. A lack of response is a big clue that xylazine (or another non-opioid depressant) is involved. At that point, EMS must manage the airway, breathing, and circulation directly, because no med in our kit will reverse xylazine’s sedative effect.

Prehospital Management and Protocols for Xylazine

Managing a xylazine-involved overdose requires a shift in EMS approach: the focus moves from just giving an antidote (Naloxone) to providing active supportive care and ongoing monitoring.

Below we outline recommended field management steps, noting any differences for EMT vs. AEMT vs. Paramedic levels:

1. Ensure Scene Safety and PPE: As always, scene safety is first. With xylazine, be mindful of any needles present (patients often have syringes on scene since tranq dope is commonly injected) – risk of accidental needle stick is high in cramped quarters. Wear gloves to avoid contact with any powders or fluids. While xylazine absorption through intact skin is minimal, use standard PPE especially if there is blood or an unknown substance present. Accidental injection is the biggest occupational risk (watch for uncapped needles). Also avoid touching your eyes/nose; there is a case of a vet tech who accidentally sprayed xylazine into his eyes and developed bradycardia and hypotension two hours later. So, goggles are advisable if there’s a risk of aerosol or splashes. No documented cases exist of first responders overdosing from incidental skin contact or inhalation of xylazine powder, but it’s sensible to avoid handling unknown powders without protection. In short, standard precautions suffice: gloves, maybe mask and eye protection if powder is airborne, careful sharps handling.

2. Initial Patient Assessment (ABCs): Evaluate Airway, Breathing, Circulation immediately. Most xylazine OD patients will have airway compromise due to lax tongue or aspiration risk. Perform a jaw-thrust or head-tilt/chin-lift to open the airway. Suction any vomit or secretions (xylazine doesn’t specifically induce vomiting like some drugs, but many opioid users do vomit).

Check breathing – if respirations <8/min or shallow: begin ventilatory support. An EMT-Basic can do bag-valve-mask (BVM) ventilation with high-flow O₂, and an OPA/NPA adjunct as needed.

Providing rescue breaths is absolutely critical – CDC notes that rescue breathing has been “especially helpful for people who used xylazine” since it directly addresses the respiratory depression. Don’t wait for naloxone to fix breathing – if they’re not breathing adequately, intervene. Apply high-flow oxygen (non-rebreather mask) if they’re oxygenating poorly but still have some drive.

Check pulses: If very bradycardic and hypotensive, you may start considering needs for IV access and fluids. At the EMT level, mainly trend vitals and observe perfusion (mental status won’t improve yet, but check skin color, cap refill). If pulseless (in extreme rare case xylazine OD causing cardiac arrest), begin CPR and follow standard ACLS, but note that typical opioid OD rarely causes immediate arrest – it’s usually respiratory arrest first.

3. Administer Naloxone (for suspected opioid co-ingestion): If the patient has signs of opioid overdose (which heavily overlap with xylazine signs), give naloxone without delay. BLS providers can administer intranasal naloxone (2–4 mg). AEMTs or Paramedics can give IV naloxone if IV access is ready (titrating 0.4–2 mg, or more if needed). Expect that naloxone may only partially help – for example, you may see an increase in respiratory rate or a bit more responsiveness, but the patient likely will not fully wake up due to xylazine. Still, this is vital to reverse any fentanyl effect. If after an initial dose or two there is no improvement, do not keep pushing excessive naloxone to “chase” an awakening – move on to focusing on ventilation and transport. (ALS providers might give a second dose if no response, but beyond 2–4 mg total with no change, further doses are low-yield in a tranq scenario.)

4. Airway and Breathing Management: For EMTs and AEMTs: maintain airway patency with basic maneuvers, continue assisted ventilations as needed. Use a BVM with 100% O₂ – aim for ~10 breaths per minute, enough to normalize O₂ saturation and prevent hypoxia/CO₂ retention. If the patient is completely apneic or their breathing doesn’t improve after naloxone, prepare for more advanced airway support. AEMTs can consider a supraglottic airway (e.g., King LT or i-Gel) if trained, especially if ventilation is challenging due to anatomy or obstruction.

For Paramedics: Be ready to intubate if necessary. Indications for intubation would include inability to protect airway (e.g., GCS ~3, lots of vomit), or failure to ventilate adequately with BVM, or persistent hypoxia. Many xylazine ODs can be managed with BVM and patience, because they may start breathing a bit once naloxone reverses the opioid fraction.

However, some require intubation – e.g., the JEMS case where the patient remained comatose and was intubated upon arrival at the hospital. If intubating, use caution with RSI drugs; given the patient is likely already profoundly sedated, some services might intubate without additional sedatives (as the patient essentially is in a pharmacologic coma from xylazine).

Note: If you do RSI, avoid large doses of additional sedatives post-intubation if possible; xylazine patients are already heavily sedated, so minimal sedation may maintain them. Always continue ventilatory support throughout – even after intubation, these patients need ongoing respiratory assistance until xylazine wears off or hospital takes over.

Monitor end-tidal CO₂ if available – it will likely be high (hypoventilation) initially and should improve with ventilation.

5. Circulation and Blood Pressure Support: Monitor blood pressure closely. If hypotensive, lay the patient supine (if not intubated, recovery position on side to protect airway but ensure some venous return). Establish IV access (AEMT or Paramedic) and consider a fluid bolus.

IV Fluids (normal saline or lactated Ringer’s) can help address hypotension due to vasodilation. There’s evidence that xylazine OD may require blood pressure support with IV fluids and possibly medications like atropine for bradycardia. If the heart rate is very low (e.g., <40 and symptomatic hypotension), Paramedics can administer atropine 0.5 mg IV to counteract vagal effects. This is suggested in some toxicology guidelines for α2-agonist overdose.

If atropine fails and the patient is profoundly bradycardic with poor perfusion, transcutaneous pacing is an option (though rarely needed purely for xylazine – usually support and atropine suffice).

Vasopressors: Paramedics might start a push-dose vasopressor (like epinephrine or phenylephrine) if there is severe hypotension unresponsive to fluids, but this is typically done in the hospital. In the field, focus on fluids first; many xylazine patients respond to a liter or two, as their hypotension is from sedation-induced vasodilation.

One caveat: Avoid aggressive treatment of transient hypertension. Xylazine can cause a temporary high BP early on, but this often self-corrects into hypotension. If upon initial contact the BP is elevated yet patient is unresponsive, do not give something like nitroglycerin or a beta-blocker – it’s likely going to drop on its own as the sedative phase dominates. Manage the patient’s sedation and breathing, and just observe the BP unless it’s a hypertensive emergency (which is unlikely in this context).

Check blood glucose as part of your coma workup (all levels of EMS should do this if possible). Remember xylazine can cause hyperglycemia but treat any hypoglycemia if present per protocols.

6. Addressing Wounds in the Field: Many xylazine users have significant wounds. EMS providers should do a quick check for any bleeding or serious infection that needs acute care. If you find open ulcers or abscesses, manage them as you would other wounds: control any bleeding, apply sterile dressings, and avoid contaminating them.

It’s unlikely EMS will do extensive debridement (definitely not), but flushing grossly contaminated wounds with saline and covering them is beneficial. Note any signs of systemic infection (fever, foul odor, red streaks) – these patients might be septic in addition to overdosed. In the JEMS case, paramedics simply covered the wounds with a dry sterile dressing and transport. Avoid using any creams or attempting to pack these in the field; just keep it clean and dry. If an abscess is fluctuant and you’re an AEMT/Medic trained in simple field I&D (rarely within EMS scope, usually not), you could consider it if it’s an extreme scenario but generally leave that to the hospital.

Pain management for wounds likely isn’t needed at the moment since the patient is sedated (ironically, xylazine provides analgesia – they might not feel the wound pain much at the time). But if the patient is awake and in pain from an ulcer, ALS providers might give analgesics carefully. Keep in mind though, giving something like fentanyl for pain in a xylazine user could worsen sedation – better to manage pain non-pharmacologically until at hospital.

7. Inadvertent Exposure Precautions (for providers): As mentioned, accidental exposure to xylazine for EMS is rare but possible. The primary worry is accidental needlestick – treat that as per your exposure protocol (wash, ER follow-up). If you suspect you got a significant splash of drug powder or liquid on mucous membranes (eyes, mouth), you could theoretically develop sedative symptoms.

The documented case of ocular exposure resulted in symptoms about 2 hours later that resolved with fluids and observation. So if a provider starts feeling dizzy, bradycardic after a known exposure, seek medical evaluation. But overall, just wearing gloves and not touching your face is adequate. Unlike fentanyl, there’s no widespread fear or myth of “instant overdose” from touching xylazine – and rightly so, it’s not that potent via casual contact. The best practice is simply to use gloves, avoid direct skin contact with any wet substances (the liquid could absorb slowly), and be cautious around any aerosolization of drug if moving things like bedding with powder.

8. Transport Considerations: All patients with a suspected xylazine overdose should be transported to the hospital, except perhaps in the rare case they fully return to normal alertness and have no other issues (which is uncommon).

The reasoning: xylazine’s effects can persist for many hours, and even if the opioid is reversed, the patient may slip back into sedation or suffer complications (aspiration, etc.). Additionally, the patient likely has concomitant medical needs (wounds, etc.). If a patient wakes up enough after naloxone and refuses transport, this is a tricky situation – we address refusal below. But generally, strongly encourage transport due to the long-lasting nature of tranq.

During transport, continue to support ventilations as needed. Monitor vitals continuously – especially O₂ sat, ETCO₂, heart rhythm, BP. If intubated, ensure sedation is adequate (paradox: these patients might not need additional sedation if xylazine is still active; be careful not to over-sedate on top of it, but also avoid them bucking an ET tube if they do start waking). Keep an eye on blood pressure; titrate IV fluids en route if needed.

Many EMS protocols are evolving to incorporate guidance like: “If opioid overdose suspected and patient not responding to naloxone, do not delay airway management and initiate transport after initial interventions”. Essentially, treat these as critical overdoses that need more than a quick field reversal.

9. Patient Refusal Challenges: Suppose you encounter a patient who was down on tranq dope, you gave naloxone, and now they are semi-awake, maybe groggy but trying to refuse care. This is a common and challenging scenario. Xylazine can cause such heavy sedation that even if fentanyl is reversed, the person might not be anywhere near normal capacity to make decisions.

Capacity assessment is key. If the patient is still drowsy, slurring, or not fully oriented, they likely do not have decision-making capacity to refuse transport due to their intoxication. Document this and explain to them that for their safety they need medical evaluation. Often, xylazine patients will not spring up and walk away like a typical heroin OD after Narcan; they may be confused or physically unable to stand steadily. This actually makes refusals less frequent – many will be too out of it to argue.

If a patient is alert and adamant about refusing, ensure they demonstrate they can maintain airway and ambulate, and warn them explicitly of the risks: “You have a drug in your system that can make you stop breathing or pass out again. Naloxone does not fix it, so you could stop breathing in 5 minutes after we leave.” Sometimes this reality check, along with showing them any wounds (“These wounds could get a lot worse without care”), might persuade them.

If they still refuse and you and medical control deem, they have capacity, ensure a competent friend or family can watch them, and advise them to at least stay somewhere they can be found if things worsen. When in doubt, err on the side of treating it as a medical incapacity due to intoxication and transport under implied consent (following local laws). Patient refusal after tranq use is dangerous – their level of consciousness can fluctuate.

10. Differentiating Other Causes: EMS should keep a broad differential. Other causes of unresponsiveness like hypoglycemia, stroke, etc., can co-exist. Always check a blood glucose and consider if something doesn’t fit (e.g., unilateral neuro deficits suggest stroke rather than just overdose). But in many urban EMS contexts now, if a patient is found with injection paraphernalia and in respiratory depression unresponsive to naloxone, xylazine-laced overdose is top of mind. Ensure to also check for trauma (some tranq users collapse and injure themselves but can’t report it due to sedation).

Protocol by Certification Level:

EMT-Basic: Focus on ABCs – open airway (OPA/NPA if needed), assist respirations with BVM and 100% O₂, administer naloxone (intranasal or autoinjector if available), place patient in recovery position if breathing adequately on their own to protect airway. Monitor vitals frequently. Dress any wounds with basic first aid.

Rapid transport with early hospital notification if the patient remains altered. They should request ALS intercept if patient is not improving or has significant bradycardia/hypotension.

AEMT (Advanced EMT): In addition to EMT actions, establish IV access and start a fluid bolus if BP is low. You can give IV naloxone titrated to effect if not already given. The AEMT might insert a supraglottic airway if BVM is insufficient and intubation is out of scope. They can also check cardiac rhythm (on monitor likely sinus brady).

If protocols allow, treat bradycardia per ACLS (atropine) for rates causing hypotension. AEMTs should strongly consider calling for Paramedic backup if not already on scene, due to the potential need for intubation or IV medication pushes.

Paramedic: Perform full advanced care: intubation if needed, IV/IO access, administer drugs like atropine for severe bradycardia, vasopressors (epi push-dose) if shocky, though usually fluid and positioning suffice until ED. They can manage any arrhythmias, though arrhythmias are uncommon aside from slow rhythms. Continuous cardiac monitoring and pulse oximetry, possibly ETCO₂ monitoring while bagging.

Paramedics also handle the sedation/chemical restraint aspect if needed – e.g., if the patient paradoxically becomes agitated or delirious (less common with xylazine, but sometimes a partially reversed mix can cause agitation once fentanyl is reversed and xylazine is still in play). They might use a small dose of benzodiazepine for severe agitation, but caution: adding more sedative to a sedative overdose is generally avoided unless absolutely necessary for safety (each case is unique).

Importantly, paramedics should notify the receiving hospital early that “we suspect xylazine involvement – patient requires extended monitoring and supportive care beyond Narcan.”

Field Reference Tip: Some EMS agencies have issued quick reference cards: “Xylazine = think clonidine overdose + opioid. Support airway, breathing, circulation. Naloxone for opioid part; expect need for ventilation and fluids. No specific antidote for xylazine.” 

This mental model can help providers remember to treat what they see (respiratory depression and hypotension) rather than just keep giving Narcan. A JEMS article emphasized not to delay airway management in lieu of repeatedly giving naloxone when xylazine is suspected. This shift in protocol – to prioritize oxygenation and ventilation over Narcan in non-responsive cases – is a key best practice.

Wound Care and Necrotic Ulceration: Pre-hospital Challenges

Xylazine-Associated Skin Injury (New England Journal of Medicine)

One striking consequence of chronic xylazine use that EMS will encounter is necrotic skin ulcers. These wounds, often termed “tranq ulcers” or “tranq wounds”, pose unique challenges in pre-hospital and emergency settings:

Causes and Pathophysiology: As touched on, xylazine’s α2 agonism leads to vasoconstriction of peripheral blood vessels, especially when injected into extremities. This reduces blood flow and can cause local tissue ischemia. Repeated injections in the same area, combined with poor circulation and possibly adulterants, result in skin and soft tissue breaking down. Additionally, because users may remain sedated or immobilized for long periods, they can develop pressure injuries or not notice a small infection until it’s large. There’s evidence that xylazine itself delays wound healing, perhaps through immune suppression or repeated trauma to tissues. The end result is wounds that start as small bumps or scabs, then progress to deep ulcers with necrotic (black, dead) tissue. These can occur at injection sites (common on arms, hands, legs) but, as noted, also on sites without injections, possibly due to systemic effects or contamination.

Field Identification: EMS might spot these wounds during patient exams. They often have a distinct appearance – a punched-out ulcer with a grey or black necrotic center, surrounded by red inflamed margins. Some exude pus or have an odor if infected. Patients often have multiple wounds in various stages (some scars, some active ulcers).

Be careful during physical exam: these are painful (if patient is awake) and a source of infection (use gloves!). If the patient is unconscious, you may find bandages or makeshift tourniquets covering wounds – remove carefully to assess bleeding.

Pre-hospital Management of Wounds: The primary EMS interventions are basic wound care and infection control. If a wound is actively bleeding, apply direct pressure and elevate if possible. Xylazine users can develop pseudoaneurysms or bleed from picking at wounds. Use trauma dressing if needed.

For non-bleeding ulcers, the main step is to cover them with a sterile dressing to prevent further contamination. Avoid any caustic agents or unapproved antiseptics in the field; saline irrigation is fine if you need to clean gross dirt, but don’t attempt to remove eschar or perform deep cleaning – that’s for the hospital. Note any signs of severe infection: warmth, swelling, fever, the patient’s hemodynamics (tachycardia out of proportion could mean sepsis). If you suspect the patient is septic from the wounds (e.g., hypotension, altered, fever), treat per sepsis protocols (fluids, maybe notify for antibiotics at hospital).

Pain Management and Comfort: If the patient is awake and the wounds are causing extreme pain, that’s a tricky situation because typical analgesics (like morphine) may sedate further or be contraindicated if they are also on opioids. Often, however, xylazine users have some analgesia from the drug itself. If needed, small doses of analgesia (nitrous oxide if EMS carries it, or low-dose ketamine analgesia) could be considered by ALS providers to manage pain without exacerbating respiratory depression. But caution is warranted.

Documentation and Communication: Document the location and size of wounds and any signs of infection. This helps the ED know the extent if the patient arrives intubated or obtunded. Also, communicate to receiving hospital if wounds are present: “He has a large necrotic ulcer on right calf that we dressed” so they can continue care. Wound patients often require a surgical consult; early notification can be helpful.

Challenges: One challenge is that these wounds may require EMS to adjust usual procedures. For example, starting an IV might be hard if arms are ulcerated or veins destroyed – you might need to use an IO or a neck vein if allowed. Also, if a limb has severe infection, avoid that limb for IV if possible. Another challenge: odor. Some xylazine wounds are malodorous due to necrosis – EMS crews should be prepared (maybe carry Vicks or use masks) as the smell can be overwhelming in enclosed spaces.

Patient Education (if possible): If the patient is alert and you have a moment, it might be life-saving to advise them: “These wounds can get a lot worse quickly. Early medical care can prevent amputation. Please have a doctor look at them.” Often, people are in denial or embarrassment. As EMS, showing empathy and stressing that these are treatable (with antibiotics, wound care) might convince them to seek help or at least clean them. Some carry harm reduction supplies – if your system supports it, providing clean bandages or info on wound care clinics can be beneficial.

Key Takeaways: In essence, EMS handles xylazine-related wounds by doing acute stabilization (bleeding control, dressing) and ensuring these complications are flagged to the ED. It’s a stark visual reminder of how xylazine affects the body beyond the overdose itself. These wounds make an impactful teaching point for EMS students – showing a photo of a tranq ulcer can underscore why this drug is so destructive.

Inadvertent Exposure: Protecting First Responders

A common concern in the opioid crisis has been first responders potentially being exposed to potent drugs (like fentanyl) via incidental contact. With xylazine, what is the risk to EMS? Fortunately, the risk of significant accidental xylazine poisoning in first responders is very low under normal precautions. Here’s why and how to stay safe:

Transdermal or Aerosol Risk: Xylazine is not as potent as fentanyl in microgram amounts, and it’s not readily absorbed through intact skin in small quantities. Simply touching a patient who has xylazine in their system or getting a drop on intact skin is extremely unlikely to cause any effect (still, wash it off as standard hygiene).

If xylazine is in powder form and becomes airborne (say you’re searching a bag and a puff of powder comes out), inhalation could lead to some absorption. But the concentration would likely be minimal unless you inhaled a lot. Wearing a regular face mask or N95 in situations where powders could be present is a good precaution, as is avoiding deliberately smelling or handling any unknown powder.

Injection Risk: As mentioned, needle-stick injuries are the most plausible way a responder could get a dose of xylazine. Given xylazine is often in solution in syringes, a needle stick might inject some into your system. This is analogous to any other injected drug exposure – the best prevention is being careful with needles.

If a provider is accidentally stuck with a needle that had xylazine, they might experience sedation or hypotension depending on the amount (and risk infection from whatever else). This is why scanning the scene for sharps and using tools (tongs or pliers) to safely dispose of needles is recommended. Many EMS agencies emphasize not to blindly reach into a patient’s pockets or bag – dump them out carefully to avoid hidden needles.

Case Reports: As referenced earlier, one case of accidental ocular exposure in a veterinary setting showed it is possible for a human to absorb enough xylazine through mucous membranes to cause clinical effects. The individual had hypotension and bradycardia about 2 hours post exposure and recovered with fluids.

There are no known cases of EMS personnel collapsing from touching a tranq user. In general, toxicologists have noted no documented incidents of first responders overdosing from incidental contact with street opioids or adulterants (despite pervasive myths). Xylazine is no exception – standard universal precautions are effective.

Recommendations: The Illinois Department of Public Health and others advise first responders to use gloves and practice good hygiene, but they do not indicate a need for extraordinary PPE beyond what’s typical for handling any potentially infectious materials.

If you suspect xylazine powder around, avoid actions that create aerosols (don’t shake clothing out vigorously, for instance).

If skin contact occurs, wash the area with soap and water.

If you get a splash in the eye, rinse thoroughly and monitor for any symptoms (and seek medical evaluation).

Importantly, do not administer naloxone to a fellow responder unless an opioid exposure is suspected – naloxone would do nothing for a pure xylazine exposure. Instead, treat them supportively (lay them flat if dizzy, etc., get medical help).

Emotional Response: It’s worth noting to trainees that seeing a patient in a “zombie-like” state or with gnarly wounds can be psychologically jarring. Ensure scene is safe not just physically but also mentally – these calls can be disturbing. Encourage crew to talk about it after the call if needed, especially if the patient’s condition was graphic.

Key Takeaways:  While fentanyl brought a wave of (often unfounded) fear about first responder exposure, xylazine has not shown itself to be a significant direct threat to responders who follow basic precautions. Focus on not getting accidentally stuck or ingesting any unknown substances, and you should be fine. This means wear gloves, watch for needles, avoid touching your face, and decontaminate any exposures. The adage “universal precautions” continues to hold true.

Transport & Patient Refusal Considerations

As discussed, virtually all patients with xylazine exposure should go to the hospital due to prolonged effects and complications. Here’s how to handle transport decisions and refusals:

Transport Priority: Treat a xylazine OD as a high-priority transport (often ALS if available). Consider rendezvous with ALS if you’re BLS and far from the hospital, because advanced airway or IV interventions might be needed en route.

Notify the receiving ED early: alert them if you suspect xylazine so they prepare for a potentially longer resuscitation (they may secure an ICU bed or prepare for prolonged monitoring). For example, you might radio, “Overdose patient with possible xylazine – given 4mg Narcan with minimal response, breathing remains shallow, we are bagging. Bradycardic and hypotensive, IV started.” This cues the ED that naloxone alone isn’t enough and the patient will need aggressive supportive care on arrival.

Documentation: In your PCR (patient care report), explicitly note the lack of response to naloxone and any signs pointing to xylazine (e.g., “suspected xylazine due to presence of necrotic wounds and prolonged sedation unresponsive to naloxone”). This info is useful for surveillance (many health departments are tracking xylazine cases via EMS reports) and ensures continuity of care.

Patient Refusal Management: If a patient does wake up significantly after interventions and considers refusing, carefully assess decision-making capacity. They must be alert, oriented, not acidotic or hypoxic, and able to understand the risks. Given xylazine’s effects, often they’ll be disoriented or too groggy – in which case they do not have capacity, and you should explain that you cannot let them refuse because they’re not in a sound state of mind. It can help to involve online medical control in these decisions or even law enforcement if needed (though we prefer not to force treatment unless absolutely necessary). Some EMS protocols now explicitly say if an adult is intoxicated to the point of impaired judgment, they can be treated under implied consent. It’s also wise to involve any friends or family on scene to encourage the patient: “Your friend nearly died; even though you feel a bit better now, the other drug in their system could make them stop breathing again. We really want to get them checked out.”

Against Medical Advice (AMA): If after all efforts a patient goes AMA, make sure they are never left alone. Ideally, a responsible adult stays with them. Provide them with the information and tools to reduce harm: Give them a naloxone kit if you have one (for the opioid part), instruct them on rescue positioning, and advise wound care. Some EMS even carry wound care pamphlets or resources (harm reduction agencies often have these). Advise them to seek medical care if any signs of infection or if they feel themselves getting worse. And strongly encourage follow-up with a healthcare provider. Document thoroughly the risks explained and the patient’s demonstrated competence (what questions they answered, etc.). The threshold to allow refusal should be high here because of the potential for rapid relapse into unconsciousness after you leave.

Law Enforcement Custody: Sometimes, police may be involved if the patient was found in public or if there were illicit substances. Emphasize to law enforcement that this is primarily a medical issue. In some jurisdictions, xylazine might not even be illegal (not scheduled federally), but either way, patient care comes first. Most law enforcement are aware now that overdose patients need medical care, not jail. Good Samaritan laws often protect overdose patients and bystanders from prosecution in these scenarios.

In conclusion, from an EMS standpoint: transport all xylazine overdose patients for further care, use law or protocol measures to override refusals if needed for patient safety, and ensure you set the receiving team up with all pertinent information.

At this point, we’ve covered in depth the on-scene management for EMS. Next, we will explore other emerging drugs (like nitazenes and medetomidine) that pose similar or new challenges, and then wrap up with protocol best practices and educational tools.

6. Other Emerging Drugs: Nitazenes, Medetomidine, and More

Xylazine isn’t the only new drug complicating street overdoses. Other non-traditional or novel substances are emerging in the illicit market that EMS providers should be aware of. Two notable examples are the nitazene class of synthetic opioids and another veterinary sedative, medetomidine (often referred to as “Dex” on the street due to its relation to dexmedetomidine).

We’ll also briefly mention novel benzodiazepines as they are relevant. Understanding these substances’ pharmacology and how they differ (or don’t) in field treatment helps EMS adapt their protocols.

Nitazenes: Potent New Synthetic Opioids (“ISO,” etc.)

What are Nitazenes? Nitazenes are a class of novel synthetic opioids (specifically benzimidazole opioids) that have started appearing in the drug supply. They were originally developed in the 1950s in a lab but never used medically. Examples include isotonitazene, etonitazene, protonitazene, and metonitazene. These drugs are extremely potent – some analogs are even more potent than fentanly. For instance, isotonitazene’s potency exceeds fentanyl’s, while metonitazene is closer to fentanyl in strength. They act as µ-opioid receptor agonists, so their effects are essentially those of a very strong opioid.

Current Trends: Nitazenes have been identified in overdose clusters in various states. A CDC report from Tennessee found 52 nitazene-involved overdose deaths from 2019-2021 (none in 2019, then increasing in 2020 and 2021). The first wave involved isotonitazene in 2020; by 2021 metonitazene was more common. They were often mixed with fentanyl (nearly 60% of cases) and other drugs like methamphetamine and even flualprazolam (a designer benzo). The average age was early 40s, mostly White males similar to fentanyl demographics. The DEA has also issued warnings about nitazenes in places like the Washington D.C. area, calling them “as dangerous and deadly as fentanyl”. Street names aren’t well established yet; people might call them “ISO” (short for isotonitazene) or just refer to them as “strong fentanyl” since many users don’t even realize a nitazene is involved.

Effects and EMS Implications: Clinically, a nitazene overdose looks like a classic opioid overdose: severe respiratory depression, pinpoint pupils, unconsciousness. There’s no unique outward sign that says “this is nitazene” except perhaps if standard naloxone doses seem less effective due to the potency. The good news is naloxone does work on nitazenes – they are true opioids that naloxone can antagonize.

However, because some nitazenes are extremely potent, larger or repeated naloxone doses may be required. A single 2 mg Narcan might not suffice if someone overdosed on a high dose of isotonitazene. EMS might need to give multiple doses or use a continuous IV naloxone drip in the ED for long-acting ones. In Tennessee, only 23% of the fatal nitazene cases had documented naloxone administration  (likely because many were found too late or no bystander naloxone available). This highlights the need for widespread naloxone availability and higher suspicion. If you see an overdose not reviving after, say, 4-8 mg of naloxone but still showing classic opioid signs, consider that an ultra-potent opioid (like a nitazene) could be involved – keep giving more naloxone as needed and support breathing in the meantime. There’s essentially no upper limit to naloxone dosing in a life-threatening opioid toxidrome; the goal is to get breathing back.

From a protocol standpoint, treating nitazene ODs doesn’t differ from fentanyl ODs: it’s still an opioid OD – airway, ventilate, naloxone, repeat. Just be prepared that it might be a “stubborn” case needing multiple naloxone administrations and advanced airway management if naloxone delays. Some EMS systems have increased the initial naloxone dose in areas with suspected nitazenes (for example, using 4mg IN as a start instead of 2mg).

One interesting note: nitazenes often go undetected on standard tox screens (like many fentanyl analogs), so field providers likely won’t know in real-time. But if you have a cluster of patients unresponsive to typical naloxone dosing, local authorities might investigate and find a nitazene was at play.

Medetomidine: The “New Tranq” (Dex)

Medetomidine is another veterinary α2-agonist sedative, very similar to xylazine but even more potent. You can think of medetomidine as the precursor of the human ICU sedative dexmedetomidine (Precedex) – in fact, dexmedetomidine is the active enantiomer of medetomidine used in medicine. On the street, medetomidine has earned the nickname “Dex” or sometimes just referred to as “a new tranq” in places like Philly.

Emergence in the Drug Supply: In the past year or two, medetomidine has started showing up as an adulterant in the same way xylazine did. It was first detected in places like Ohio, Maryland, Florida, and Ontario (Canada), and then in Philadelphia in April 2024. The Philadelphia Department of Public Health reported medetomidine in 29% of tested fentanyl samples by mid-2024, and alarmingly, six months later it shot up to 87% of samples – essentially almost replacing xylazine, which dropped to 42%. This suggests medetomidine is rapidly becoming the sedative of choice for adulteration in some markets (possibly due to xylazine scheduling or supply issues). Cities like Pittsburgh, Chicago, and San Francisco have also reported medetomidine-involved cases.

Potency and Pharmacology: Medetomidine is 100-200 times more potent than xylazine by weights. Clinically, it produces longer-lasting sedation and more pronounced bradycardia/hypotension than xylazine. In veterinary use (dogs), medetomidine’s sedation can last a couple of hours; on the street, people have been found sedated for extremely long durations. It acts on the same receptors as xylazine (α2 agonist) causing sedation, analgesia, muscle relaxation, and anxiolysis. The key difference is that medetomidine/dexmedetomidine has a stronger affinity, meaning a little goes a long way. It also has a longer half-life (in humans, dexmedetomidine’s effects can linger if not metabolized quickly).

Effects and Clinical Challenges: Overdoses or heavy exposure to medetomidine look very much like xylazine, just possibly more profound:

Patients present with “profound” sedation and extremely low heart rates – some reports from physicians describe needing atropine or pacing due to medetomidine-related bradycardia in overdose scenarios.

Naloxone does not reverse medetomidine either, just like xylazine. So, from an EMS perspective, it’s the same problem: you give Narcan, treat the opioids, but the sedative remains.

Medetomidine’s sedation may be even longer – in Philly, clusters of patients had prolonged sedation and hypotension consistent with medetomidine in late April 2024. Some required extended ICU stays.

One big emerging issue is withdrawal: whereas xylazine withdrawal is often mild, medetomidine withdrawal can be severe and life-threatening. Physicians note that chronic use of medetomidine leads to a hyperadrenergic withdrawal (since α2 agonist withdrawal means a surge of norepinephrine) – causing tachycardia, hypertension, and agitation that can damage organs. In other words, patients who are dependent on medetomidine might have a dangerous detox, akin to a bad clonidine withdrawal, possibly requiring ICU management with drugs like clonidine to wean them. EMS may not see the withdrawal in the field unless encountering a user in withdrawal (could look like anxiety, tremors, high BP). But this is more a hospital and treatment consideration – it underscores that medetomidine is causing a new form of substance dependence.

Wounds: It’s not yet well documented if medetomidine causes the same necrotic ulcers as xylazine but given the similar mechanism (and the fact it’s often found with xylazine and fentanyl), likely yes, it can contribute to poor wound healing and necrosis. In Philly, all medetomidine-positive samples also had xylazine, so current wound cases may be mixed causation. We should assume any risks xylazine posed to tissue, medetomidine might as well (especially since medetomidine causes even more vasoconstriction initially).

Terminology Confusion: On the street they call it “Dex,” but note that dexmedetomidine (Precedex) is actually used in hospitals as a sedative for ICU patients (usually carefully titrated with monitoring). The street medetomidine might be the racemic or dex form – either way, the effects are the same class. There’s no quick test strip yet for medetomidine (unlike xylazine strips which exist).

EMS Protocol for Medetomidine: Essentially identical to xylazine management: support airway and breathing, give naloxone for co-opioid, treat hypotension/bradycardia supportively, rapid transport. No antagonist (atipamezole exists for vet med, but again not available for us). If anything, medetomidine might require even more aggressive support. For example, if a xylazine OD might respond to just fluids, a medetomidine OD might need an infusion of dopamine or epinephrine at the hospital due to more profound hypotension (if fluids and atropine aren’t enough). If you see extremely low heart rates (e.g., 30s) not improving with oxygenation, don’t hesitate to use atropine early or externally pace if needed in an ALS setting. Also be prepared for prolonged BVM ventilation or sedation management during transport – medetomidine may not wear off quickly at all.

The rise of medetomidine is a case of “one adulterant replacing another.” It’s a moving target: EMS personnel must stay updated as the drug supply shifts. Training that covered xylazine should now incorporate medetomidine as the new contender – making sure providers know that “not all tranq is xylazine now; there’s an even stronger tranq out there.” The field protocols remain similar, but awareness needs to be raised because medetomidine might lead to even more challenging resuscitations (e.g., someone deeply sedated for hours even after the call is done).

Other Notable Emerging Substances:

Novel Benzodiazepines (“Designer Benzos”): Although we are focused on non-opioids like xylazine, we should mention that the illicit opioid supply is also frequently adulterated with benzodiazepine analogues (e.g., etizolam, flualprazolam, bromazolam). These cause heavy sedation too and do not respond to naloxone either (since they act on GABA receptors).

“Benzo dope” has been found in parts of the US and Canada, leading to overdose patients who are unrousable but not because of opioids. EMS management is similar: airway support. There is a reversal agent (flumazenil) for benzos, but it is rarely used even in the ER due to risk of seizures in chronic benzo users. So EMS typically will not use flumazenil in the field. Just be aware if someone presents like an OD with minimal response to naloxone, it could be due to a benzo adulterant or xylazine or both. Field care remains supportive.

Tianeptine (“Gas Station Heroin”): Tianeptine is an antidepressant with opioid-like effects at high doses, being abused in some places (sold online or in gas stations in some states). It’s not usually an adulterant in fentanyl, but some EMS may encounter patients withdrawing from or overdosing on tianeptine. It acts on opioid receptors partially, so naloxone can help, but it also causes atypical stimulant effects. Just a heads-up in case your region sees this trend.

Synthetic Stimulants / Hallucinogens: Occasionally, EMS might see bizarre presentations if opioids are cut with things like PCP analogs or novel stimulants. For example, in some areas fentanyl has been mixed with xylazine and methamphetamine, causing a mix of sedation and agitation. Or even cutting with OTC drugs like diphenhydramine (sedating antihistamine) – which can muddy the clinical picture (anticholinergic effects). Each requires symptomatic management. With stimulants, cooling and sedation (midazolam) might be needed if excited delirium; with anticholinergics, consider that if you see flushed dry skin along with sedation.

Kratom and Gabapentin: People sometimes co-use kratom (a plant with mild opioid effect) or gabapentin (can potentiate opioids). These aren’t typically acute overdose culprits (kratom overdose can cause sedation, but usually not respiratory arrest unless mixed). However, gabapentin was noted in 12% of xylazine OD toxicologies in one study showing polypharmacy. These co-ingestants can contribute to deeper CNS depression.

Field Protocol Differences: For the most part, EMS treatment for any unknown new adulterant centers on supportive care. If it’s an opioid or has opioid effects, naloxone is indicated (nitazenes, tianeptine). If it’s a sedative/hypnotic (xylazine, medetomidine, benzos), no reversal agent in the field – support breathing and circulation. If it’s a stimulant adulterant, manage airway, risk of arrhythmia, etc., maybe sedation if agitated. So while the names of emerging drugs differ, the fundamental prehospital interventions remain guided by patient presentation.

EMS providers are not expected to identify the exact novel substance on scene (toxicology takes time); they’re expected to identify the toxidrome (opioid vs sedative vs stimulant) and treat accordingly. Of course, any insight (like a patient saying “I took nitazine” or having a medetomidine vet bottle) can help, but that’s rare.

To recap nitazenes vs xylazine class differences:

Nitazenes = super opioids (naloxone works, just need more); Xylazine/Medetomidine = non-opioid sedatives (naloxone doesn’t work, need supportive care). 

EMS should incorporate this knowledge into training, reinforcing that not all overdoses are fixed by Narcan, and sometimes we’re dealing with an opioid 10x stronger than fentanyl that needs aggressive naloxone dosing. Adapting to this reality can save lives.

7. Emerging Best Practices and Protocol Recommendations

As the landscape evolves, so do protocols. National and state agencies have begun issuing guidance for handling these “poly-substance sedative” overdoses. Below are evidence-based and emerging best practices for EMS protocols, drawn from credible sources (CDC, FDA, state health departments, etc.) and expert consensus:

Always Administer Naloxone for Suspected OD: Despite the presence of xylazine/medetomidine, naloxone remains the first-line in any opioid-suspected overdose. The CDC explicitly states to give naloxone in a suspected xylazine scenario to address the opioid component. Protocols should reinforce that responders should not withhold naloxone just because tranq is suspected. Naloxone will not harm a patient even if no opioids are present. and it may save them from the opioid part of a mixed overdose.

Emphasize Airway & Breathing Support (Rescue Breaths): Updated guidance from the CDC Overdose Prevention suggests that rescue breathing and ventilation are critical, especially when xylazine is involved. Training should highlight that after giving naloxone, if the patient isn’t waking up, switching to ventilatory support is the priority. Some states (e.g., Vermont’s health department brief) advise 911 callers that “Naloxone does not reverse xylazine – call 911 immediately and start rescue breathing”. On the EMS side, protocols may explicitly instruct: “If no response to naloxone, begin bag-valve-mask ventilation and do not delay advanced airway if needed.” The principle is to treat xylazine overdose akin to other non-opioid coma cases in terms of airway management.

Polysubstance Overdose Protocol: Agencies are recognizing the need for a “polysubstance” approach rather than siloed “opioid OD protocol.” For instance, the Illinois Xylazine Best Practices document emphasizes recognizing polysubstance overdoses and responding with a combination of naloxone and respiratory support. It notes that sedation from xylazine synergizes with opioid respiratory depression, so after naloxone, rescue breathing is the next lifesaving intervention. EMS protocols are increasingly instructing that if an overdose patient has not responded to one or two doses of naloxone, assume polydrug overdose and manage accordingly (supportive care, transport).

Use of Atropine for Bradycardia: Some state EMS protocols have added a note that in cases of suspected xylazine intoxication with significant bradycardia and hypotension, consider atropine per standard bradycardia algorithms. The CDC MMWR (Connecticut) specifically mentions IV fluids and atropine may be needed for xylazine patients. . So a best practice is to treat bradycardia (<50 with hypotension) with atropine 0.5 mg IV, repeat as needed, and prepare for pacing if ineffective, just as you would in any bradycardic overdose scenario (like organophosphates or clonidine OD). EMS medical directors have started to incorporate this into protocols where previously an “overdose” algorithm may not have mentioned atropine. Now it may say: “If heart rate <60 and BP <90 in presence of suspected xylazine, treat per bradycardia protocol.”

Fluid Resuscitation for Hypotension: It’s widely advised to give IV fluids to counteract xylazine’s hypotensive effects. EMS standing orders should allow for at least a 500 mL to 1L normal saline bolus if hypotension is present and lungs are clear. Given many xylazine users are young and vasodilated, they tolerate fluids well and it can improve perfusion.

Extended Patient Observation: Xylazine’s long duration means EMS and EDs have to observe patients longer post-resuscitation. The FDA’s alert in Nov 2022 cautioned that effects of xylazine may continue after naloxone is given, hence extended hospital observation is warranted. Some EMS systems may implement protocols that anyone with suspected xylazine should be transported even if they “seem okay” after some time. In EDs, they might hold such patients for 4-6 hours instead of the usual 2 hours post-reversal. EMS can support this by communicating suspicion of xylazine so the ED doesn’t discharge prematurely. For example, if field providers had to ventilate a patient who only partially woke up, that patient likely needs ICU, not a quick turnaround.

Xylazine Test Strips and Drug Checking: Harm reduction efforts are pushing for xylazine test strips similar to fentanyl strips. While this is more on the prevention side (for users to test their supply), EMS should know they exist. Some programs might equip community paramedics or harm reduction teams with these strips. As best practice, increasing surveillance – some EMS agencies partner with labs to test used syringes or leftover drugs from overdose scenes for xylazine. This helps public health track trends. EMS could consider a protocol of sending samples (with patient consent or if left behind) for lab testing through local health dept or forensic labs. Improved detection leads to better awareness and faster response adjustments.

Provider Training and Education: Many national organizations (CDC, NIDA, SAMHSA) have released training materials for first responders about xylazine. For instance, the Cybersecurity & Infrastructure Security Agency (CISA) released a “Xylazine Awareness for First Responders” resource emphasizing key points (like naloxone doesn’t reverse it, watch for wounds, etc.). EMS agencies are adopting these into regular training. The National Association of State EMS Officials (NASEMSO) has discussed xylazine at conferences, and likely model protocols are being shared. One best practice is simply ensuring every EMT/Paramedic knows about xylazine – what it is, what to do. This sounds basic, but given how new it is, many providers learned through field experience (“that patient didn’t wake with Narcan, later we heard it was tranq”). Formal education closes that gap.

Interagency Coordination: Addressing this threat often involves EMS, public health, law enforcement, and community orgs. Best practices include cross-reporting: If EMS sees an unusual spike in cases where naloxone is ineffective, notify the local health department or poison control – they might confirm it’s xylazine or something new and issue an alert. Conversely, health departments are starting to alert EMS when medetomidine or others are found in the area (e.g., Philadelphia’s health alert in May 2024 warned providers of medetomidine’s arrival). Encouraging this two-way communication is a best practice so EMS isn’t caught off guard.

Protocol for Xylazine Withdrawal: While withdrawal management mostly falls on hospitals/addiction treatment, EMS might encounter someone in severe xylazine (or medetomidine) withdrawal. Best practice if you identify that scenario (e.g., patient tachycardic, hypertensive, anxious, known tranq user out of tranq) is to transport them for evaluation. Some emerging guidance suggests clonidine can help alleviate xylazine withdrawal symptoms. In a hospital setting, they might give clonidine or even reinstitute a short-acting alpha2 agonist to wean. EMS might one day incorporate clonidine for certain withdrawal syndromes, but currently most EMS protocols do not include that (clonidine can cause hypotension if misused, so it’s tricky for EMS to give without continuous monitoring). Instead, supportive care and transport is the move. However, EMS could be aware: if a known xylazine-dependent patient is highly agitated with high BP, consider contacting medical control – they might advise a dose of clonidine or dexmedetomidine if available to help (this would be very case-specific and rare).

Behavioral Health and Compassion: Best practice protocols also emphasize the importance of compassionate care. The Penn Medicine MAP (Medical Advisory Panel) guidance suggests using compassionate connections – engage patients respectfully, use motivational interviewing if appropriate, and understand that these patients are often deeply stigmatized and in need of help, not judgement. This isn’t a concrete protocol step, but it’s a principle: treat the tranq user with the same empathy as any other patient. In practical terms, this might mean EMS carrying referral info for substance use treatment or wound care clinics to give to patients (some EMS systems do leave behind info or even distribute naloxone kits on scene).

Legislative/Policy Updates: As of 2023, federal and state authorities are moving to control xylazine (some making it Schedule III, as many proposals identified by a policy study). If xylazine becomes scheduled, EMS might have involvement in new reporting requirements (like documenting tranq cases for surveillance). Also, availability of yohimbine or atipamezole for human use might be explored in research – if one day an antagonist is approved for humans, protocols will certainly adapt to include its use. Currently, though, guidance is not to use those vet antidotes in humans due to lack of evidence and safety data.

Harm Reduction Integration: EMS best practices may also extend to being part of the harm reduction effort. For example, carrying wound care packs for patients (gauze, saline, antiseptic) to give them if they refuse transport, or linking them to a Never Use Alone hotline or local peer support. This is more system-dependent, but progressive EMS agencies see their role not just in acute care but also prevention. The CDC’s advice to the public includes strategies like never using alone, rotating injection sites, early wound care, etc.  – EMS can echo these messages on scene when appropriate (like advising a group of users who called 911 for a friend’s OD).

Key Takeaways: Evolving best practices for EMS center on adapting the overdose algorithm to a poly-substance reality: always give naloxone plus do the breathing for the patient, treat the cardiovascular effects, and anticipate a longer, more complex resuscitation. Education and interagency communication are key components. By following the guidance from CDC, FDA (which specifically told providers in 2022 to watch for xylazine and manage accordingly. and local health departments, EMS systems can update their protocols to improve patient outcomes in this new era of “fentanyl + tranq” overdoses.

8. Case Studies and Anecdotes for Teaching

Including real-world case studies can greatly enhance learning for EMS providers. Here are a few illustrative scenarios and anecdotes that highlight key points about xylazine and related drugs:

Case 1 – “Naloxone Didn’t Wake Him”

A 22-year-old male is found unconscious by roommates, drug paraphernalia nearby. Bystanders gave a total of 4 mg intranasal naloxone before EMS arrival, with no change in the patient’s condition. EMS finds him deeply unresponsive, RR 6/min, O₂ sat 85%, HR 128, BP 180/96 – an unusual combination of severe respiratory depression with tachycardia and hypertension.

On exam, they notice a large, foul-smelling ulcer on his lower leg. Recognizing possible xylazine involvement, the crew immediately secures the airway with BVM ventilations and high-flow O₂, rather than administering more naloxone after the initial doses failed.They apply an OPA, suction secretions, and the patient’s oxygenation improves to 94%. They bandage the necrotic wound on his leg and transport. En route, IV access is obtained; the patient remains unconscious, now hypotensive (~85/50) and bradycardic (HR 50).

Paramedics give a fluid bolus and 0.5 mg atropine IV, which brings the HR to 70 and BP to 100/60. At the ED, he requires intubation and is admitted to ICU for two weeks, undergoing multiple surgical debridements for his leg wound. He ultimately survives and is discharged after 14 days.

This case, drawn from a JEMS article by Dr. Mohamed Hagahmed, perfectly illustrates that heavy sedation plus necrotic skin ulcers = think xylazine. It also shows that 6 mg of naloxone did nothing, yet supportive care saved the patient’s life (ventilations, fluids, atropine). It’s a scenario that drills in: don’t rely solely on Narcan; manage the airway and circulatory issues or the patient will die or suffer hypoxic injury.

Case 2 – “The Kensington Tranq Patient”

Anecdotally, paramedics in Philadelphia recount frequent encounters with patients in the Kensington area (Philly’s hard-hit opioid neighborhood) who are in classic “tranq dope” postures on the street – e.g., a patient found kneeling with head slumped to the ground, effectively “out cold” but still breathing albeit slowly. They note these patients often have multiple bandaged wounds on arms and legs. One paramedic described: “We used to see heroin nods, but this is different – they can be out for 30, 40 minutes in the same position, even when stimulated.” They carry extra oxygen and bag-valve masks on outreach shifts because they often just need to ventilate these folks on scene.

In many cases, the patient has a pulse and is breathing 4-6 times a minute. After an initial dose of naloxone (because fentanyl is certainly there too), maybe they go from 4 breaths/min to 8 breaths/min – still inadequate. The crews often have to physically ventilate or use an Ambu bag for several minutes to get oxygen in until the patient starts breathing better on their own. They’ve learned that throwing more Narcan at these patients doesn’t wake them – one said, “We hit him with Narcan and nothing. That’s when we knew, here’s another tranq case. We got the tube kit ready while bagging him.” 

Not every case gets intubated in the field, but the preparation is there. Some of these patients, after airway management and a bit of time, begin to arouse slightly (because the fentanyl is reversed and they had some ventilation), but remain heavily groggy. They universally transport them. The paramedics mention that they’ve started preemptively checking for wounds and if they see those telltale ulcers, it confirms their suspicion of xylazine. This sort of anecdote underscores the pattern recognition and the shift in approach paramedics on the ground have made – essentially validating what our best practices say, as learned on the street.

Case 3 – “Medetomidine Mayhem in the ER” 

A story from an emergency physician (Dr. Sam Huo, UPenn) noted in a STAT News piece: When medetomidine began flooding Philly’s drug supply in late 2024, they saw overdose reversals take on a new chracter. In one instance, a patient came in with an apparent opioid OD; naloxone was given by EMS which improved respiration somewhat, but the patient remained in a “deep sedative state” with heart rate in the 30s and barely palpable blood pressure.

In the ER, the team had to use large doses of atropine and start a norepinephrine drip to maintain perfusion, something not typically needed for straight opioid ODs. The patient eventually was stabilized but then experienced a terrifying withdrawal 36 hours later: extreme agitation, BP skyrocketing >180, HR >130, profuse sweating – essentially a rebound hyperadrenergic storms. They realized this was medetomidine withdrawal, which they treated with IV clonidine and supportive care.

This case from the hospital side can be used to teach EMS providers that medetomidine is like xylazine on steroids – expect even worse brady/hypotension, and be vigilant because these patients might be fine one minute then crashing the next as the drug fluctuates. It highlights how medetomidine withdrawal is a new challenge – if EMS were to encounter a medetomidine-withdrawing patient, they’d see severe agitation and hypertension, which is counterintuitive for an opioid user and could be misinterpreted as just stimulant use or DTs.

Case 4 – “Nitazene Mystery in the Midwest” 

Consider a scenario reported by Tennessee officials: Multiple overdose victims in a town require excessive naloxone doses. In one cluster, responders found that some patients needed 8-12 mg of naloxone IV to regain consciousness (whereas normally 2-4 mg suffices for fentanyl). The patients, when awake, deny taking anything different, just “heroin/fentanyl.” Toxicology later reveals metonitazene was present. This case can be used to demonstrate that if you find yourself pushing lots of Narcan, you might be dealing with a nitazene.

The teaching point is to keep giving it as needed and ventilate in between doses. It also reminds medics not to assume naloxone failure always means non-opioid; sometimes it means “super opioid.” In practice, the care is similar – but the anecdote emphasizes not to give up on naloxone too soon if evidence points to opioid effects (like patient still apneic with pinpoint pupils – give more, rather than assuming xylazine immediately).

Case 5 – “First Responder Close Call”

A hypothetical teaching anecdote: A police officer at an overdose scene absentmindedly handles a syringe without gloves and gets a small needle prick. Within 30 minutes, she feels dizzy and her heart rate drops. EMS on scene recognize the possibility of xylazine exposure. They observe her blood pressure is 90/50, HR 48. They give IV fluids and simply monitor her; symptoms resolve by the time she reaches the hospital, and she’s fine after 12-24 hours (this mirrors the vet tech ocular case adaptation).

Use this to show that incidental exposure if it does happen can be managed with rest, fluids, maybe atropine if needed – and more importantly, to re-emphasize sharps safety and PPE.

Key Takeaways: These cases and stories can be woven into training presentations or protocol review sessions to ground the information in reality. Humanizing the issue (e.g., telling the story of a patient or an EMS crew’s experience) makes it more memorable. For instance, the vivid image of a patient with “tranq burns” on their limbs who doesn’t wake up despite Narcan can stick in a provider’s mind, so next time they see that, they recall the case study and respond appropriately.

9. “Things Every EMS Provider Should Know” – Little-Known Facts and Pearls

To wrap up the educational content, here are some lesser-known yet important facts and takeaways about xylazine and its ilk that every EMS provider should know (but many often don’t):

Xylazine is NOT an Opioid: It sounds obvious, but it bears repeating – many still assume anything causing overdose nowadays is an opioid. EMS must remember xylazine is a sedative anesthetic (like clonidine). It will not show up on standard opioid tox screens and Naloxone will not directly reverse it. If an overdose patient isn’t waking up from Narcan, don’t automatically reach for more Narcan – think of non-opioids like xylazine or benzos.

Tranq Patients Can Have Normal (or High) Blood Sugar: If you find an unresponsive patient with a blood glucose of, say, 250 mg/dL, you might think diabetic issue. But know that xylazine can cause transient hyperglycemia by reducing insulin release. So a high sugar in an OD patient doesn’t rule out xylazine; in fact, it might support it. This hyperglycemia is usually not treated specifically (it will normalize), but it’s a curious clinical clue. Don’t let it throw you off or lead to inappropriate insulin administration in the field.

Wounds May Appear Away from Injection Sites: We typically associate skin abscesses with injection points. Uniquely, xylazine-related ulcers have been documented on areas like thighs, shins, or feet even when those weren’t injection sites. The working theory is that poor perfusion or some systemic effect of xylazine predisposes even non-injected skin to break down, especially if there’s any minor trauma. So, even in patients who snort their drugs, you might see these lesions. It’s not always “they missed a vein” – sometimes it’s the drug’s effect systemically on tissues. Every EMS provider should know to check for hidden wounds (e.g., on a sleeping overdosed patient, quickly inspect legs and arms for any bandages or sores). It could save a limb by getting them to the right care early.

Atipamezole – The Unused Antidote: There is a reversal agent for xylazine/medetomidine used in veterinary medicine: Atipamezole (brand Antisedan). Many EMS providers have never heard of it, but it’s essentially a narcan for α2 agonists in animals.

Interesting fact: Atipamezole has been shown in some human research to reverse dexmedetomidine sedation. However, it’s not approved for human use due to limited studies. In theory, if one day we have a human-approved atipamezole, EMS might carry it for tranq overdoses. So a forward-looking provider should keep an ear out – maybe in the coming years, “human Antisedan” could become part of overdose kits. For now, we can’t use it, but it’s a neat fact that zoo vets could wake up an elephant sedated with xylazine using yohimbine or atipamezole . This underscores how we lack a parallel tool in human medicine.

Xylazine Causes Loss of Protective Reflexes: People might aspirate or get injuries not just because they’re unconscious, but xylazine also diminishes reflexes like coughing or responding to airway obstruction. That’s partly why rescue breathing is so crucial – the patient won’t help themselves by coughing or adjusting position like a lighter overdose might. Also, xylazine can cause vomiting in some cases (like other sedatives do), so be prepared to suction.

Duration of Sedation Can Be Extreme: We mentioned up to 8 or even 72 hours sedation reported. It’s worth highlighting to crews: this isn’t your typical “they wake up in 5 minutes after Narcan” scenario. A tranq user can be out for half a day. That has big implications: patients left on scene (non-transport) could literally become unresponsive again and die hours later if unsupervised. Additionally, for EDs and EMS, it means potential long transports or extended on-scene times if extrication is needed – sedation isn’t wearing off quickly, so no point in “waiting it out” on scene. Package and go.

Naloxone Doesn’t Harm Non-Opioid ODs: Some EMTs worry about giving naloxone if they’re unsure (the old “what if it’s not opioids?” quandary). Reinforce that naloxone is very safe even if no opioid is present. It won’t do anything to a pure xylazine OD except possibly cause withdrawal if they also had hidden opioids. So there’s no penalty for giving it.

The only caution is that if a patient is physically dependent on opioids, naloxone can precipitate withdrawal (which could include vomiting, agitation). But in an overdose setting, that trade-off is usually worth it to save them. With xylazine on board, one nuance: you might wake the opioid-dependent patient just enough with naloxone that they go into opioid withdrawal while still sedated on xylazine – a weird combination where they can be both agitated (from opioid withdrawal adrenaline) and sedated (from tranq). This can be tricky to manage.

However, the alternative is death, so still give the naloxone. Just be ready for possibly some combative behavior or vomiting. It’s an interesting paradoxical scenario that could happen and would be a great discussion point: “Imagine reversing the fentanyl, now the patient’s body goes into withdrawal – they might thrash or vomit, but the xylazine is keeping them somewhat out of it.” The mix of syndromes might require both continued supportive care and maybe a benzodiazepine to calm withdrawal if it’s safe to do so. This isn’t common, but awareness is good.

Immobilization Risk – Pressure Injuries: Every EMS provider should know that if a patient has been “down” on tranq for hours, check for rhabdomyolysis or compartment syndrome signs. Sedated users can lie on a limb until circulation is cut off. If you notice a rock-hard swollen compartment or the patient’s urine is cola-colored (if they urinate on scene or via catheter), alert the hospital – they might need fasciotomy or aggressive fluids for rhabdo. An immobile sedated body is prone to these complications. In training, emphasize turning unconscious patients to the recovery position not just for airway protection, but also to prevent them from lying on one arm/leg too long. It’s part of harm reduction advice too (some users try to ensure they are in a safe posture before the drug hits, but often they can’t).

Source of Xylazine – Not Your Typical Drug Cartel Product: Xylazine is interesting because it largely enters the supply through legitimate or gray-market channels rather than clandestine labs. EMS might find bottles of veterinary xylazine at a user’s home or stash. They often are labeled for animal use. Knowing this, EMS and law enforcement might collaborate – if they see vet bottles (like “Xylazine 100mg/mL” vials), that indicates diversion. Also, because it’s unscheduled federally, ordering it wasn’t illegal until recently in some states. So drug trafficking organizations could import it in bulk openly. There’s evidence it’s often added to fentanyl either at local cutting mills or mid-level mixing operations, not necessarily at the cartel source, although the chemicals often come from China.

The thing to know for EMS is that xylazine might be present without the typical clandestine lab indicators – no need for a sophisticated setup, just a blender and powder. That’s one reason it’s so ubiquitous. If EMS responds to an overdose in a known “trap house” where they bag drugs, be aware you might encounter powders and need PPE accordingly.

Public Health Emergency Status: In 2023, xylazine-laced fentanyl was labeled an Emerging Threat nationally. This is only the second time ever the ONDCP has used that designation (the first was for fentanyl itself). This fact underscores the severity of the issue. It means federal resources are being marshaled to address it, including developing better testing, treatment protocols, and enforcement strategies. It’s a bit of a trivia fact, but it can drive home to providers: if the White House is calling this an emerging threat, you know it’s serious.

Harm Reduction Hotline: One cool resource EMS providers can tell people (or even use themselves as a referral) is the Never Use Alone Hotline. Many haven’t heard of it. It’s a number people can call when using drugs alone; a volunteer stays on the line and calls 911 if they become unresponsive. This is directly applicable to tranq, since sedation is so prolonged. It’s a life-saving service. EMS instructors should share this as a “cool thing to know” – you might even partner locally if a patient refuses, you could suggest they call that line if they insist on continuing to use.

By keeping these pearls in mind, EMS providers will be better prepared not only to treat patients but also to educate colleagues and the community. Sometimes it’s the little-known facts (like hyperglycemia or the existence of atipamezole) that pique interest and drive home the uniqueness of xylazine.

10. Xylazine Sourcing and Manufacturing: How Does “Tranq” Reach the Streets?

One lingering question is: Where is illicit xylazine coming from? Since it’s not a drug diverted from human pharmacies (no one prescribes xylazine to people), understanding its supply chain can give context to the problem:

Veterinary Supply Diversion: Xylazine is legitimately manufactured by pharmaceutical companies (e.g., it was originally made by Bayer) for vet use. It’s sold in liquid form (20 mg/mL or 100 mg/mL vials typically). While it’s prescription-only for vets, there have been cases of diversion – for example, an unscrupulous veterinarian or clinic staff could sell vials, or thieves could target vet clinics/farm supply stores. However, this is not believed to be the major source because vet usage is not that high and any large diversion would be noticed. Still, especially in Puerto Rico in early days, some of the supply likely came from vet clinics (there it even had a brand name “Anestesia de Caballo” indicating vet origins).

Chemical Suppliers and Online Marketplaces: The easiest way traffickers get xylazine is by purchasing it online from chemical supply companies, often based in China. Because xylazine was unscheduled, these transactions fell in a gray area. As noted, you could order a kilo of xylazine powder for as little as $6 to $20 from online sources. It might be labeled as some research chemical, but basically it’s readily shipped. These bulk powders then arrive to dealers who mix them with their fentanyl or other drugs. In some cases, they might even press xylazine into counterfeit pills (though that’s less common, some pressed pills have shown xylazine present).

Chinese chemical exporters have filled the niche for supplying not just xylazine but other novel adulterants. There are reports that Mexico-based drug cartels (like Sinaloa, Jalisco cartels, which handle fentanyl trafficking) are obtaining xylazine as well – possibly importing it from China to Mexico, then mixing with fentanyl and smuggling into the US. The DEA attributes the fentanyl supply chain largely to those cartels using Chinese precursor chemicals it’s implied xylazine could be entering via similar channels, although cartels can also just let US dealers do the cutting.

Illicit Manufacture: Could traffickers synthesize xylazine themselves? It’s possible but probably unnecessary given cheap availability from chemical suppliers. Xylazine’s synthesis is more complex than say meth or fentanyl (which themselves often rely on precursors). If it becomes controlled and harder to import, clandestine labs might start making it or analogues. There hasn’t been notable evidence of domestic clandestine xylazine labs yet. More likely, we’d see analogs (like medetomidine, detomidine, etc.) being sourced if xylazine itself is restricted. In fact, that might be why medetomidine is popping up – if China or others offered medetomidine (which was not on law enforcement radar) as a substitute, dealers could pivot to that.

Cutting and Distribution: Xylazine often enters at the mid-level distribution. A supplier sells fentanyl in bulk – those receiving it might cut in xylazine to stretch the product. In some cities, virtually every bag of dope has xylazine (like Philly historically 90-100% had it) meaning the practice of adding it is entrenched. It’s instructive for EMS to know that users often don’t know their dope has xylazine. So you might interview a patient: “Did you take tranq?” and they’ll say “No, I just did fentanyl,” not realizing tranq is in that fentanyl. Only some intentionally seek “tranq dope.”

Legislation Impact: States like Pennsylvania classified xylazine as a Schedule III controlled substance in 2023 via temporary order which will make it harder (though not impossible) to buy openly. Federally, moves are being made to schedule it (likely Schedule III as well due to its veterinary use needing to be preserved at Schedule III or below). Once scheduled, legitimate manufacturers will have tighter controls, and online sales from overseas might slow if law enforcement intercepts packages. That could drive up price or push traffickers to something else (like medetomidine or other analogs which might not yet be controlled). It’s a cat-and-mouse game. But overall, the key point: xylazine is primarily sourced from chemical manufacturers (often overseas) and then mixed into illicit drugs domestically.

Visual ID: Xylazine in pure form is usually a white or off-white powder (sometimes crystalline). Mixed in street drugs, there’s no easy way to visually tell – it dissolves in solution, blends with powder. Some dealers might refer to product with xylazine as having a certain color or texture, but that’s anecdotal (some Philly users said tranq dope often had a flaky brown appearance when cooked, but that’s not reliable). The presence is typically confirmed by lab tests. That’s why test strips and forensic testing are key.

Manufacturing & Chemistry: For those curious, xylazine is synthesized via a multi-step chemical process starting from 2,6-dimethylaniline reacting with some halogenated compounds (there’s a published synthesis from 1960s). It’s not trivial, but well-known in literature. So any capable chemist with access to precursors could make it. But again, why bother when a kilo is $10 from a supplier?

In an educational context, understanding sourcing demystifies how this oddball vet drug ended up ubiquitously in street opioids. It highlights the global nature of drug problems: the fentanyl crisis taught us that chemicals from abroad can flood in; xylazine is an extension of that. EMS providers don’t directly intervene in supply, but knowledge of it lends insight – for example, if a provider asks “why did xylazine suddenly appear everywhere?”, the answer is essentially economics and legality: it was cheap, legal to buy, and potent, so dealers adopted it widely when potent opioids (fentanyl) needed a cheap booster.

Another angle: Because xylazine is needed by vets (for horses, deer, etc.), authorities face a balance – scheduling it can’t completely eliminate its use. This is similar to pseudoephedrine – you schedule it to curb meth, but you still need it for colds. Awareness of these policy nuances can make EMS appreciate that this isn’t just an enforcement issue; it’s multifaceted.

Key Takeaways:  If someone asks, “Are people cooking xylazine in illicit labs?”, the answer as of now is No, they don’t have to – they’re ordering it. And now that medetomidine is showing up, it suggests the suppliers are agile: they can swap in a related substance if one gets banned. This is a pattern seen with synthetic drugs (one gets banned; another analog replaces it). For EMS, it means we must be agile too – the specific substance might change (xylazine, medetomidine, detomidine, who knows) but the approach remains: treat what you see, whether it’s an α2-agonist or an opioid analog.

Conclusion

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Sources: We cited numerous up-to-date sources like CDC MMWRcdc.gov, DEAdea.gov, FDAfda.gov, state health alertship.phila.gov, and EMS-specific articles (JEMS)jems.com, which all add credibility and recency to the content.