Researchers have identified bradycardia—an abnormally low heart rate–as a symptom of xylazine-opioid overdose. This breakthrough finding from the Icahn School of Medicine at Mount Sinai may help emergency medicine physicians detect whether patients have been exposed to xylazine, a drug that is increasingly found as an additive to the illicit fentanyl supply, particularly in the Northeast.
Accurate detection of xylazine overdose could help physicians take the correct steps to save lives following an overdose. The results were published in the January 13 issue of Addiction.
"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," says lead researcher Jennifer Love, MD, Assistant Professor of Emergency Medicine at the Icahn School of Medicine at Mount Sinai. "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."
Xylazine is a powerful animal sedative and pain reliever that is approved strictly for veterinary use. However, 25 percent of the U.S. fentanyl supply includes xylazine. Xylazine overdose can cause adverse events such as severe skin lesions, sedation, hypothermia, and heart issues. Since it's not authorized for humans, there are knowledge gaps about how xylazine impacts patients.
Mount Sinai researchers wanted to better understand the effects that xylazine can have on people who use opioids. Through collaboration and partnership with the American College of Medical Toxicology's Toxicology Investigators Consortium, they conducted a prospective observational study of 1,289 adult patients with suspected opioid overdose in the emergency departments at 10 health care institutions across the United States between September 2020 and September 2023. Waste blood samples from all sites were de-identified and sent for toxicology testing at a specialized forensic toxicology lab to identify xylazine and other substances. They compared patients with xylazine and an illicit opioid detected in their blood samples to patients with only an illicit opioid detected. Then, they used statistical analysis to determine which vital signs, such as heart rate and blood pressure, were associated with xylazine detection, and if a certain age, race, gender, or area of the country had more xylazine-opioid overdoses.
Xylazine was detected in 238 patients. Of those patients, 6 percent had bradycardia at their arrival to the emergency room, compared to only 2 percent of patients without xylazine, a statistically significant difference. Patients with xylazine-fentanyl overdose were twice as likely to have bradycardia compared to those without xylazine.
"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," adds Dr. Love.
Additionally, 75 percent of the patients with xylazine were located in the northeastern United States. The likelihood of xylazine detection was 60 percent lower in the Midwest, 70 percent lower 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," says senior author Alex Manini, MD, MS, Professor of Emergency Medicine and Director of the Center for Research on Emerging Substances, Poisoning, Overdose, and New Discoveries at the Icahn School of 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."
Researchers are currently studying xylazine's association with patient outcomes such as length of stay and intensive care unit admission. Additional studies are evaluating the relationship between measured blood concentrations of xylazine and vital signs like heart rate and blood pressure.
Funding for this study was provided by the National Institute on Drug Abuse, a division of the National Institutes of Health, and the Centers for Disease Control and Prevention.
About the Mount Sinai Health System
Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with 48,000 employees working across seven hospitals, more than 400 outpatient practices, more than 600 research and clinical labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time—discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.
Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients' medical and emotional needs at the center of all treatment. The Health System includes approximately 9,000 primary and specialty care physicians and 10 free-standing joint-venture centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida. Hospitals within the System are consistently ranked by Newsweek's® "The World's Best Smart Hospitals, Best in State Hospitals, World Best Hospitals and Best Specialty Hospitals" and by U.S. News & World Report's® "Best Hospitals" and "Best Children's Hospitals." The Mount Sinai Hospital is on the U.S. News & World Report® "Best Hospitals" Honor Roll for 2025-2026.
