Exploring Xylazine: A Medical and Public Health Imperative
Originally published in the New England Journal of Medicine on April 26th, 2023.
What is Xylazine?
Xylazine, also known as "Anesthesia de Caballo" or "Tranq," was declared an emerging national threat by the White House Office of National Drug Control Policy on April 12, 2023. It's an Alpha-2 agonist belonging to the same drug class as clonidine and dexmedetomidine (Precedex). Initially investigated as an antihypertensive for human use, it was discontinued due to adverse effects. However, in 1972, Xylazine was approved exclusively for veterinary use.
How Did Xylazine Enter the United States?
The first reported use of Xylazine in the U.S. occurred in Puerto Rico in 2001. It likely entered the drug supply as an additive to fentanyl and has since been found predominantly in areas such as Philadelphia and Connecticut.
How Widespread is Xylazine in the Drug Supply?
By 2021, Xylazine was detected in 90% of illicit drug samples in Philadelphia. Forensic toxicology reports indicated that 36 of 49 states had identified Xylazine in seized illicit drugs. As of March 2023, Xylazine has been found in drug seizures across 48 states.
How Does Xylazine Work?
Xylazine inhibits the release of norepinephrine and epinephrine, resulting in effects that last longer than fentanyl.
Expected Toxidrome/Side Effects (Frequency % of complaint in patients)
Sedation, analgesia, and euphoria
Miosis
Acute drug-induced encephalopathy (90%)
Hypotension (25%)
Bradycardia (50-75%)
Respiratory depression (due to the presence of opioid compounds) (20-50%)
Withdrawal symptoms with chronic use, if abruptly discontinued
Does Naloxone Work?
Naloxone may reverse respiratory depression caused by opioids but does not reverse the effects of Xylazine. Currently, no specific reversal agent is available for Xylazine.
How is Xylazine Treated?
Treatment focuses on supportive care, including:
Airway management, breathing support, and circulatory stabilization
Atropine drip for bradycardia
Mechanical ventilation
Peripheral vasopressors (e.g., norepinephrine, vasopressin, phenylephrine)
Managing Acute Withdrawal
Managing acute withdrawal remains a topic of debate. Some intensive care units are trialing clonidine (with a risk of hypotension), lofexidine (which has fewer side effects), and dexmedetomidine.
What Makes Xylazine Unique?
One of the distinctive features of Xylazine is the development of necrotic skin ulcers, often occurring near the injection site. The underlying pathophysiology of these ulcers is still unclear.
For images of these wounds, click here.
Read the full article here.
Resources:
Lankenau, S. E., Wenger, L. D., Silva, K., Kral, A. H., & Lambdin, B. H. (2023). The Emerging Threat of Xylazine in the U.S. Drug Supply. New England Journal of Medicine, 389(9), 802-804. https://doi.org/10.1056/NEJMp2303120