Perioperative Pain in the Era of Emerging and Unregulated Substances: Recognition, Risk Assessment, and Management

This review examines the perioperative implications of selected substances in the contemporary unregulated drug supply and outlines a physiology-based approach to preoperative assessment, risk recognition, and postoperative pain management.

Patients may be exposed intentionally or unknowingly to fentanyl and nitazenes, xylazine and medetomidine, kratom and concentrated 7-hydroxymitragynine products, tianeptine, phenibut, and other psychoactive substances. Clinically important patterns include respiratory depression, prolonged sedation, bradycardia, hypotension, opioid tolerance, withdrawal, and difficult postoperative pain. Polysubstance exposure, uncertain product composition, and limitations of routine toxicology screening may complicate identification of the responsible substance. Perioperative assessment should emphasize specific, nonjudgmental history taking, recognition of physiologic patterns, and individualized risk stratification rather than reliance on identification of a specific substance. Perioperative planning should integrate physiologic findings with the limitations of toxicology testing and distinguish surgical pain from tolerance, withdrawal, opioid-induced hyperalgesia, and delirium. Awareness of a geographically variable and rapidly evolving drug supply is increasingly important for safe perioperative care.