Researchers from the Icahn School of Medicine at Mount Sinai have identified bradycardia, or an abnormally slow heart rate, as a key clinical sign of overdose involving xylazine mixed with opioids. This finding could assist emergency physicians in detecting xylazine exposure in patients who present with suspected opioid overdoses, especially given the rising presence of xylazine as an additive in illicit fentanyl supplies across the Northeastern United States.
Xylazine is approved only for veterinary use as a sedative and pain reliever but has been increasingly detected in street drugs. About 25 percent of fentanyl samples in the U.S. contain xylazine, raising concerns about its effects on humans. Because bedside tests for xylazine do not exist and detection requires specialized toxicology labs, clinicians have had limited means to recognize exposure during acute care.
"People using opioids do not intentionally seek out substances like xylazine, but are inadvertently exposed to them, and we still don't know all of the potential health effects that these novel substances might have for patients," said Jennifer Love, MD, Assistant Professor of Emergency Medicine at Mount Sinai and lead researcher. "There's also no way to test patients at the bedside for xylazine, so doctors in the emergency department have no way of knowing if a patient has been exposed to this drug in addition to fentanyl or other illicit opioids – they require a blood test for detection that's sent to a specialized toxicology lab. Therefore, being able to associate a clinical sign, like a slow heart rate, with xylazine following an overdose can be helpful to doctors in the emergency room. They can provide harm reduction counseling for patients about adulterants and resources like drug testing strips, which allow patients with substance abuse disorders to test their drugs for these adulterant substances."
The study analyzed data from 1,289 adult patients with suspected opioid overdose across ten U.S. hospitals between September 2020 and September 2023. Blood samples were anonymized and tested for various substances at a forensic laboratory. Of those tested, 238 were found positive for both xylazine and an illicit opioid.
Bradycardia was observed in 6 percent of patients who tested positive for xylazine upon arrival at the emergency department compared with only 2 percent among those without xylazine exposure—a statistically significant difference. Patients experiencing overdose from both fentanyl and xylazine were twice as likely to show bradycardia compared to those exposed only to opioids.
"Within this niche subgroup of patients who were exposed to xylazine-adulterated fentanyl and had an overdose, bradycardia is the only significant 'signal' we have found so far of relating blood test results to a clinically meaningful marker for physicians when it comes to symptoms," Dr. Love said.
Geographically, most cases involving xylazine (75 percent) occurred in the Northeast region. The probability of detecting xylazine was much lower elsewhere: 60 percent less likely in the Midwest, 70 percent less on the West Coast, and 97 percent lower in the Southeast.
"This study demonstrates xylazine's continued predominance in the Northeast and identifies an important association between xylazine exposure and decreased heart rate following overdose," said Alex Manini, MD, MS, senior author and Professor of Emergency Medicine at Mount Sinai. "Results of the study help build a foundation for understanding a toxic syndrome, or 'toxidrome,' from xylazine-adulterated fentanyl overdose. Additionally, knowing that a routine clinical measurement, heart rate, is associated with exposure to xylazine in overdose can empower emergency medicine clinicians to improve care for patients at the bedside."
The research team continues investigating how exposure affects outcomes such as hospital stay length and intensive care admissions.
Funding support came from both the National Institute on Drug Abuse (a division of NIH) and the Centers for Disease Control and Prevention.
