Surgical Challenges and Harm-reduction Strategies in Xylazine-associated Wounds: A Systematic Review.

Background: Xylazine, a veterinary sedative not approved for human use, has emerged as a dangerous adulterant in the illicit opioid supply and is now linked to severe, progressive necrotic wounds. These lesions often occur at noninjection sites, exhibit atypical healing patterns, and are commonly complicated by infection, osteomyelitis, and delayed presentation. This study characterizes the clinical features, management strategies, and outcomes of xylazine-associated wounds to inform triage and harm-reduction efforts. Methods: A systematic review was conducted in accordance with preferred reporting items for systematic reviews and meta-analyses guidelines and registered with PROSPERO (CRD420251000303). Searches of PubMed, Embase, and Web of Science were completed through April 2025. Nineteen studies comprising 92 patients were included. Descriptive statistics and Fisher exact tests were used to evaluate associations between clinical variables. Results: Among 27 patients with detailed case-level data, all had extremity involvement (100%), with bone or tendon exposure in 56% and osteomyelitis in 30%. Surgical management occurred in 78% of patients, including grafting (41%), free flap reconstruction (11%), and amputation (26%). Algorithm-guided care, documented in 56%, was significantly associated with both bone or tendon exposure ( Conclusions: Xylazine-associated wounds are a distinct and increasingly prevalent condition. These findings support early surgical triage and structured, harm-reduction care models to improve outcomes for medically and socially vulnerable patients.