New trends in the overdose epidemic: postural impact on abusers of fentanyl and xylazine and clinical and forensic implications.

The illegal drug trade has changed dangerously since xylazine, a veterinary α2 adrenergic agonist, has become a common additive in illegally made fentanyl, creating the "tranq dope" mix. Together, they cause a synergistic central nervous system and respiratory depression that is more severe than that observed with opioid toxicity alone. This raises important questions about awareness, stigma, and clinicians' responses. A scoping review was performed in accordance with PRISMA-ScR guidelines, utilizing a PCC-structured research question. Studies examining fentanyl and/or xylazine exposure with clinically or toxicologically significant data were searched in PubMed and ScienceDirect. 38 studies were included, most from North America, including case reports, retrospective studies, narrative reviews, animal studies, qualitative research, and toxicological analyses. Co-exposure to fentanyl and xylazine has been linked to severe necrotic cutaneous ulcers, unique postural phenomena like the forward-flexed "fentanyl fold," acute muscle rigidity, including Wooden Chest Syndrome, and synergistic respiratory depression. Naloxone reverses the opioid component but does not counteract the sedative effects of xylazine, making overdose management more difficult and necessitating multimodal strategies like wound care, oxygenation support, and increased drug-checking services. Exposure to fentanyl-xylazine calls into question established models of opioid overdose and necessitates coordinated clinical and public health interventions. To combat this rapidly evolving threat, stigma must be reduced, harm reduction infrastructure expanded, and prospective research funded.