Levine et al. raise the concern about overstating the risks associated with acute xylazine use and assert that xylazine doses that are taken may be lower than those required to cause acute harm. However, the amount of xylazine observed in tested samples of street drugs is highly variable and rapidly changing. Samples with the same stamp tested in Philadelphia varied in xylazine concentration from 19% to 45%,1 and the average xylazine purity of tested samples in Philadelphia rose from just over 25% in early 2021 to nearly 40% in late 2022.2 Furthermore, the fatality risk from opioids is increased when the opioid is consumed with other sedative drugs.3 Finally, the cited study reports on adverse outcomes that occurred after patients had arrived in the emergency department (ED).4 This study did not capture data from those who died before ED arrival, avoided the ED for fear of acute withdrawal symptoms, or left before formal admission. Also, the key significant difference shown in this study between persons testing positive and those testing negative for xylazine was administration of cardiopulmonary resuscitation (CPR). In light of the respiratory challenges associated with xylazine, CPR may have been differentially administered before ED arrival. Still, we applaud this study because we are in the early stages of learning about the harms associated with xylazine. More definitive longitudinal studies will take time, and the recent national response plan calls for key basic and applied research.
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