Department of Emergency Medicine, Penn Center for Addiction Medicine and Policy, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
Center for Healing, Cooper University Health Care, Cooper Medical School of Rowan University, Camden, NJ.
Ann Emerg Med. 2024 Jul;84(1):20-28. doi: 10.1016/j.annemergmed.2024.01.041. Epub 2024 Mar 16.
Used as a veterinary sedative and not approved for human use, xylazine has been increasingly linked with opioid overdose deaths in the United States. A growing number of people have been exposed to xylazine in the illicit opioid supply (especially fentanyl) or in other drugs, particularly in some areas of the Northeast. Xylazine is an α-2 adrenergic agonist that decreases sympathetic nervous system activity. When combined with fentanyl or heroin, it is purported to extend the duration of the opioid's sedative effect and to cause dependence and an associated withdrawal syndrome; however, data to support these concerns are limited. Despite the escalating frequency of detection of xylazine in people with nonfatal and fatal opioid overdose, direct links to these outcomes have not been identified. Because the strongest causal link is to fentanyl coexposure, ventilatory support and naloxone remain the cornerstones of overdose management. Xylazine is also associated with severe tissue injury, including skin ulcers and tissue loss, but little is known about the underlying mechanisms. Nonetheless, strategies for prevention and treatment are emerging. The significance and clinical effects of xylazine as an adulterant is focused on 4 domains that merit further evaluation: fentanyl-xylazine overdose, xylazine dependence and withdrawal, xylazine-associated dermal manifestations, and xylazine surveillance and detection in clinical and nonclinical settings. This report reflects the Proceedings of the National Institute on Drug Abuse Center for the Clinical Trials Network convening of clinical and scientific experts, federal staff, and other stakeholders to describe emerging best practices for treating people exposed to xylazine-adulterated opioids. Participants identified scientific gaps and opportunities for research to inform clinical practice in emergency departments, hospitals, and addiction medicine settings.
作为一种兽医镇静剂，尚未获得美国食品药品监督管理局批准用于人体，苯环己哌啶（xylazine）与美国阿片类药物过量死亡的关联性日益增强。越来越多的人在非法阿片供应（尤其是芬太尼）或其他药物中接触到苯环己哌啶，尤其是在东北部的一些地区。苯环己哌啶是一种 α-2 肾上腺素能激动剂，可降低交感神经系统的活性。当与芬太尼或海洛因联合使用时，据称它会延长阿片类药物镇静作用的持续时间，并导致依赖性和相关戒断综合征；然而，支持这些担忧的数据有限。尽管在非致命和致命阿片类药物过量的人群中检测到苯环己哌啶的频率不断上升，但尚未确定与这些结果的直接联系。由于与芬太尼共同暴露的关联最强，呼吸支持和纳洛酮仍然是治疗过量的基石。苯环己哌啶还与严重的组织损伤有关，包括皮肤溃疡和组织损失，但对其潜在机制知之甚少。尽管如此，预防和治疗策略正在出现。苯环己哌啶作为一种掺杂物的意义和临床影响主要集中在 4 个领域，值得进一步评估：芬太尼-苯环己哌啶过量、苯环己哌啶依赖和戒断、苯环己哌啶相关的皮肤表现以及临床和非临床环境中的苯环己哌啶监测和检测。本报告反映了国家药物滥用研究所中心临床试验网络召集临床和科学专家、联邦工作人员和其他利益攸关方的会议记录，以描述治疗接触苯环己哌啶掺杂物阿片类药物的人的新兴最佳实践。与会者确定了科学差距和研究机会，以为急诊科、医院和成瘾医学环境中的临床实践提供信息。
