Manifestations of potential xylazine withdrawal: A retrospective cohort study with nested case series.

Purpose: The alpha-agonist xylazine is an increasingly common adulterant of illicitly manufactured fentanyl. A potential xylazine withdrawal syndrome (XWS) is poorly characterized. We assessed for XWS.

Methods: We conducted a retrospective cohort study of all hospitalized patients with urine GC-MS xylazine testing performed at three academic hospitals in Philadelphia, PA from 3/2022-2/2023. We used linear and logistic regression to compare peak systolic blood pressure, peak heart rate, and intensive care unit (ICU) admissions for patients with vs. without xylazine detected. Additionally, addiction specialist physicians assessed for candidate signs and symptoms of XWS (otherwise unexplained agitation, elevated blood pressure or heart rate, diaphoresis, tremor) using chart review.

Results: Of 121 xylazine tests, each among unique patients (mean age 44.6 years, 33.1 % female), 73 (60 %) were positive. Xylazine detection was not associated with differences in peak systolic blood pressure or heart rate, but was associated with lower odds of ICU admission (aOR 0.24, 95 % CI 0.09-0.60). Among 73 patients with xylazine detected, chart review determined 54 (74.0 %) did not have candidate signs of XWS, 12 (16.4 %) were indeterminate, and 5 (6.8 %) were excluded due to severe critical illness. Two patients (2.7 %) had otherwise unexplained blood pressure and heart rate elevation consistent with possible XWS. Co-occurring opioid, benzodiazepine, and alcohol withdrawal were common.

Conclusions: In a cohort of hospitalized patients, there was no association between xylazine detection and vital sign instability, xylazine detection was associated with lower ICU admission rate, and chart review did not detect distinct signs or symptoms of XWS.