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Drug overdose deaths with xylazine involvement have multiplied, with age-adjusted death rates 35 times higher in 2021 than in 2018, the CDC reported.

The age-adjusted rate of drug overdose deaths involving the animal sedative, also known as "tranq," rose from 0.03 per 100,000 people to 1.06 per 100,000, Merianne Rose Spencer, PhD, MPH, a researcher at the CDC's National Center for Health Statistics in Hyattsville, Maryland, and co-authors reported in .

"Although the rates are fairly low, there is a drastic rise over the time period," Spencer told 番茄社区app. "It really highlights that we are seeing an increased rise in drug overdose deaths involving xylazine in the U.S. in the past couple of years."

The number of such deaths rose from 102 in 2018 to 3,468 in 2021, among the 106,699 total drug overdose deaths in the U.S. in 2021, according to the . While the data provided the first national estimate of drug overdose deaths involving xylazine from NVSS data, it aligned with increases seen in state data, for example, the report noted.

Almost all drug overdose deaths involving xylazine also involved fentanyl by 2021 (99.1%, up from 97.1% in 2018). The second most frequent concomitant drug was cocaine, involved in 35.1% of 2021 xylazine cases; taking over from heroin as the third most commonly implicated was methamphetamine, in 18.8% of cases.

Spencer noted, however, that the categories were not mutually exclusive. "Ultimately, it does highlight that xylazine is not acting alone, [it] is most often involved with another drug or possibly mixed or laced with another drug as part of the drug overdose death."

While never approved for human use, xylazine has increasingly been found adulterating other drugs, particularly fentanyl. It slows breathing and heart rate, lowers blood pressure to unsafe levels, complicates efforts to reverse opioid overdoses with naloxone (Narcan), and can lead to serious flesh wounds.

Alex Manini, MD, of the Icahn School of Medicine at Mount Sinai in New York City, noted similarly high proportions of co-involvement of fentanyl and xylazine in overdoses in another by his group, but emphasized the role of fentanyl in these deaths.

"Patients who came to the emergency department with xylazine plus fentanyl for some reason had lower incidence of cardiac arrest and coma compared to fentanyl without xylazine," Manini noted. Though the exact reasons for this finding are still unclear, it "drives home the point that fentanyl is really the fatal toxin here."

"While this does not suggest that xylazine itself is protective," he added, "it certainly suggests that the toxicity of xylazine is much less than the toxicity of fentanyl in an acute overdose situation."

Manini said that much remains to be learned about xylazine, including its human half-life, the dose that results in severe sedation, withdrawal effects, and its chronic toxicity including skin lesions and necrotic lesions beyond the injection site.

Still, he said "that shouldn't necessarily take away from the fact that good CPR for first responders should include naloxone, because over 99% of the samples included fentanyl." He argued that communities should also employ harm reduction strategies like offering xylazine test strips.

Spencer's report utilized data from NVSS death certificate records, which include all death certificates that states report to a national system. Mentions of xylazine and its potential misspellings were identified in the death certificate text, along with other involved drugs. Population estimates came from early estimates of U.S. census data.

Xylazine overdoses rose particularly sharply among men over the 2018-2021 period, ending at 1.55 per 100,000 versus 0.57 per 100,000 women. Rates of drug overdose involving xylazine were highest among 35-44 year olds and lowest among those 24 and younger.

Xylazine-involved overdose deaths increased among all race and Hispanic-origin groups. Incidence was highest among Black people, with an increase from 0.68 to 1.82 per 100,000 from 2020 to 2021.

Geographically, the region containing Delaware, the District of Columbia, Maryland, Pennsylvania, Virginia, and West Virginia had the highest rate of drug overdose deaths involving xylazine, with 4.05 deaths per 100,000 people. It was lowest in the region containing Arkansas, Louisiana, New Mexico, Oklahoma, and Texas, at 0.15 deaths per 100,000. However, two of the 10 regions did not have enough xylazine-related deaths reported to meet reliability criteria.

One limitation was that reporting practices in death investigations may vary by jurisdiction across the U.S. Substances tested for in autopsies, the tests that are used, and whether testing is performed under a given set of death circumstances could affect how deaths involving xylazine are reported and change the distribution of such deaths.

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