TO THE EDITOR: As Gupta et al. make clear in their Perspective article (June 15 issue),1 illicit opioids are increasingly being adulterated with xylazine. Although we agree that it is important to be aware of xylazine, we disagree regarding the potential dangers associated with acute overdose. Gupta et al. state that xylazine intoxication may result in central nervous system depression, hypotension, and bradycardia. Although that’s mechanistically true, the doses required to produce sedation in animals (0.5 to 1.0 mg per kilogram of body weight) are typically much greater than those present in adulterated opioids. Thus, it is not clear that xylazine-contaminated opioids will be dangerous acutely. A recent multicenter study involving patients who presented to U.S. emergency departments with acute toxic effects of opioids noted similar clinical measures in patients with xylazine use and in those without use, but there were significantly lower rates of cardiac arrest and coma among patients who used xylazine.2 We are not suggesting that xylazine itself is protective, but rather that the acute toxicity of xylazine may be less than that of fentanyl, so the adulteration of opioids with xylazine may not be as dangerous acutely as was initially thought.
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