No Scientific Evidence Shows that Xylazine Causes Death or Skin Necrosis

Figure: skin necrosis, xylazine, death, contaminated drugs, needles, fentanyl, tranq, skin rotting, overdoses, tranq dope, wounds, antihypertensive, sedation, clonidine, dexmedetomidine, norepinephrine, analgesia, hypotension, bradycardia, opioids, antidote, ulcerations, infections, abscesses, blood vessels, vasoconstriction, perfusion, comatose, cardiopulmonary arrestFigureRecent headlines about the supposed effects of the so-called zombie drug xylazine have been apocalyptic: “The horrific risk of xylazine, the flesh-destroying drug making fentanyl even deadlier”—The Guardian “Flesh-rotting ‘zombie drug’ tranq takes over”—New York Post “Tranq, the new ‘zombie’ drug that causes skin rotting, is fueling overdoses across the U.S.”—Fortune The key terms about this drug, often called by the street names tranq or tranq dope, are “flesh-destroying” and “skin-rotting.” It is true that the presence of xylazine in samples of street drugs has skyrocketed in recent years: The drug had been identified in samples of illicit drugs in 48 states by March 2023, and it was detected in more than 90 percent of illicit drug samples in Philadelphia in 2021. (CDC. Nov. 28, 2023; http://tinyurl.com/rfjtxw2n; Philadelphia Department of Public Health. http://tinyurl.com/2tv55jc8.) It is also true that people who inject illicit drugs often develop severe infections and wounds at the site of injection. Given these truths, it is inevitable that some users of drugs contaminated or adulterated with xylazine will develop impressive wounds. Author Assumptions But is xylazine actually the cause? Are the sensationalist claims in the media of xylazine being a flesh-rotting drug based on science or are they arble-garble? Xylazine was first studied in the 1960s as a potential antihypertensive medicine but never approved for human use because of disqualifying side effects such as excessive sedation. It was later approved as a veterinary tranquilizer. Xylazine, an α2-agonist with an action similar to that of clonidine or dexmedetomidine, inhibits the release of norepinephrine and other neurotransmitters from presynaptic nerve endings. Effects include sedation, analgesia, hypotension, bradycardia, and respiratory depression, especially when combined with opioids such as fentanyl. It has no reliable antidote or reversal agent. Users ingest, smoke, snort, and inject (intravenously, intramuscularly, and subcutaneously) xylazine. The question of whether xylazine itself causes severe dermal wounds is still controversial. Two recent articles spell out the opposing sides of this argument. Authors from the White House Office of National Drug Control Policy wrote that xylazine is associated with severe necrotic skin ulcerations, which are “different from the wounds commonly seen in people who inject drugs [because] tissue injury may occur at or remote from an injection site and irrespective of the mode of use.” (N Engl J Med. 2023;388[24]:2209; http://tinyurl.com/bdd7uc9s.) That would support the position that xylazine caused the skin wounds if this were true, but the only reference offered for any of this is a 2022 case report citing a 1988 paper (Cureus. 2022;14[8]:e28160; http://tinyurl.com/33vn97c4) about the veterinary use of xylazine that contains nothing about ulcers, wounds, necrotizing infections, tissue injury, or abscesses. (J Vet Pharmacol Ther. 1988;11[4]:295.) The paper contains photos of impressive leg wounds on a 37-year-old woman who injected fentanyl regularly. The wounds were described as foul-smelling with purulent drainage and involving bone. Cultures grew multiple organisms. Interestingly, there were no tests for xylazine, and the authors just assumed that it was present. No Proof An opposing view was offered in a recent editorial by Robert S. Hoffman, MD, who argued that “it is more likely that contaminated drugs and needle use cause the cutaneous findings associated by too many sources with xylazine.” (Clin Toxicol [Phila]. 2023;61[12]:1013.) He pointed out that the drug is frequently injected into animals without causing severe skin wounds and that skin wounds in humans injecting xylazine commonly yield positive bacterial cultures. No mechanism by which xylazine could cause skin necrosis has been established. Some propose that the drug might injure blood vessels or cause vasoconstriction, decreasing perfusion of vulnerable dermal tissue, but this is still pure speculation. Dr. Hoffman also noted that it has not been established that xylazine—rather than the other drugs involved—caused or even contributed to the deaths even though it was detected in a large number of postmortem samples from overdoses. I side with Dr. Hoffman in this debate. I am not aware of any scientific evidence convincingly indicating that xylazine causes or contributes to death or severe skin necrosis. None of this changes the essentials of clinical management of drug overdoses. You won't really know if xylazine is present when a patient comes in comatose or in cardiopulmonary arrest, and you don't really care. Naloxone will not reverse the effects of xylazine, but it should be given because of the high probability that opioids are also involved. Basic supportive and wound care don't change whether xylazine is on board. News items have recently appeared noting increased detection of xylazine in drug supplies from Canada, the United Kingdom, and Milwaukee County, WI. The possible adverse effects of xylazine will continue to be a concern, but it is important that we all clearly understand what is known and not known about the drug. DR. GUSSOW is a voluntary attending physician at the John H. Stroger Hospital of Cook County in Chicago, an assistant professor of emergency medicine at Rush Medical College, a consultant to the Illinois Poison Center, and a lecturer in emergency medicine at the University of Illinois Medical Center in Chicago. Follow him on X @poisonreview, and read his past columns at http://tinyurl.com/EMN-Gussow. Share this article on X and Facebook. Access the links in EMN by reading this on our website: www.EM-News.com. Comments? Write to us at [email protected].

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