Abstract
Xylazine is a centrally acting alpha-2 adrenergic agonist commonly used with fentanyl in illicit drug mixtures, yet its withdrawal profile remains poorly characterized. We report a case of a 35-year-old man with polysubstance use, significant for fentanyl with xylazine and bipolar disorder. He presented with seizure-like activity and agonal breathing, requiring intensive care unit admission. The patient's persistent hypertension, agitation, and autonomic dysregulation were inconsistent with typical opioid withdrawal or sepsis. Initial management with sedatives and multiple antihypertensives was ineffective. Agitation improved with dexmedetomidine, whereas blood pressure and autonomic control were achieved after initiation of a transdermal clonidine patch, followed by transition to oral clonidine with tapering. The adjunctive use of gabapentin, lacosamide, and quetiapine helped manage psychomotor agitation and generalized pain. The patient recovered to his baseline and was discharged to an outpatient rehabilitation program. This case highlights the importance of recognizing xylazine withdrawal as an independent toxidrome requiring targeted alpha-2 agonist therapy and supports evidence-based, multidisciplinary collaboration for symptom control and clinical stabilization.