Opioid overdoses involving xylazine in emergency department patients: a multicenter study

Abstract

Introduction

Illicit opioids, consisting largely of fentanyl, novel synthetic opioids, and adulterants, are the primary cause of drug overdose fatality in the United States. Xylazine, an alpha-2 adrenergic agonist and veterinary tranquilizer, is being increasingly detected among decedents following illicit opioid overdose. Clinical outcomes in non-fatal overdose involving xylazine are unexplored. Therefore, among emergency department patients with illicit opioid overdose, we evaluated clinical outcome differences for patients with and without xylazine exposures.

Methods

This multicenter, prospective cohort study enrolled adult patients with opioid overdose who presented to one of nine United States emergency departments between 21 September 2020, and 17 August 2021. Patients with opioid overdose were screened and included if they tested positive for an illicit opioid (heroin, fentanyl, fentanyl analog, or novel synthetic opioid) or xylazine. Patient serum was analyzed via liquid chromatography quadrupole time-of-flight mass spectroscopy to detect current illicit opioids, novel synthetic opioids, xylazine and adulterants. Overdose severity surrogate outcomes were: (a) cardiac arrest requiring cardiopulmonary resuscitation (primary); and (b) coma within 4 h of arrival (secondary).

Results

Three hundred and twenty-one patients met inclusion criteria: 90 tested positive for xylazine and 231 were negative. The primary outcome occurred in 37 patients, and the secondary outcome occurred in 111 patients. Using multivariable regression analysis, patients positive for xylazine had significantly lower adjusted odds of cardiac arrest (adjusted OR 0.30, 95% CI 0.10–0.92) and coma (adjusted OR 0.52, 95% CI 0.29–0.94).

Conclusions

In this large multicenter cohort, cardiac arrest and coma in emergency department patients with illicit opioid overdose were significantly less severe in those testing positive for xylazine.

Keywords:

• Opioids
• fentanyl
• adulterants
• xylazine
• toxicosurveillance

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Author contributions

AFM, ML, KA, JB, AJK, BKL and PW conceptualized the study. AFM was primarily responsible for funding acquisition. AJK, BKL and SEW were responsible for toxicologic specimen data analysis and acquisition, while KA, AFM and the ToxIC study group were responsible for clinical data acquisition. JSL, ML, CVT and AFM conducted formal data analysis. JSL and ML wrote the original manuscript draft, and all authors were responsible for manuscript review and editing.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

Research reported in this publication was supported by the National Institute on Drug Abuse of the National Institutes of Health under Award Number R01DA048009 (PI: Manini). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. JSL is a research fellow in the Mount Sinai Clinical Scientist Training Program for Emergency Care Research [NIH1T32HL160513, NHLBI]. BKL, AJK and SEW are employees of NMS Labs which complete the toxicologic specimen testing for this study.