Introduction
History of Drug Adulterants and Overdose
Xylazine Overview
Pharmacodynamics and Pharmacokinetics
Adverse Effects of Xylazine
Xylazine Effects
Demographics and Trends
Mixed Perspectives on the Effects of Xylazine in Case Reports
Management of Xylazine Misuse and Withdrawal
Author, year published, and citation | Study title and description | Results | Conclusions |
---|---|---|---|
Delcher et al. (2023) [51] | Xylazine-involved fatal overdoses and localized geographic clustering: Cook County, IL, 2019–2022 This study conducted a geographic analysis to better identify the spatial distribution of xylazine-involved fatal overdoses compared to other substances in Cook County, IL | Analysis showed that in 2019–2022 in Cook County, IL, 94.4% of xylazine-positive overdoses contained fentanyl. The study was unable to locate high-risk clustering of xylazine-involved fatal overdoses but presented evidence that they occurred closer in proximity of up to 16 miles compared to fentanyl overdoses | Xylazine fatal overdose incident locations exhibited localized clustering primarily relative to fentanyl overdoses, but clusters were not precisely detected at these scales |
Sibbesen et al. (2023) [50] | Characteristics of xylazine-related deaths in West Virginia-Xylazine-related deaths This study conducted a large analysis comparing the toxicological findings between xylazine and nonxylazine deaths between 2019 to mid-2021 in West Virginia | Analysis showed 117 of the 3292 drug deaths involved xylazine, increasing from 1% in 2019 to 5% in mid-2021. Xylazine decedents primarily had co-intoxication with fentanyl, followed by methamphetamines. A significantly greater history of drug or alcohol misuse and hepatic disease was noted in xylazine decedents | Identification of xylazine is steadily increasing in West Virginia, especially co-intoxication with fentanyl |
Karissa et al. (2023) [49] | Illicitly Manufactured Fentanyl-Involved Overdose Deaths with Detected Xylazine—United States, January 2019-June 2022 This report uses data from the CDC’s State Unintentional Drug Overdose Reporting System (SUDORS) to describe illicitly manufactured fentanyl (IMF) involved overdose deaths with and without xylazine detected that occurred during January 2019-June 2022 | Among 20 states and the District of Columbia, the monthly percentage of IMF-involved deaths with xylazine detected increased from 2.9 to 10.9%. Xylazine was detected in a higher percentage of jurisdictions in the Northeast and lower in the West US Census Bureau regions. Finally, demographic characteristics, drug co-involvement, and circumstances were similar among IMF-involved deaths with and without xylazine detected | No demographic groups are disproportionately affected by xylazine, and certain drugs are not more often used with IMF products versus without xylazine |
Korn et al. (2021) [48•] | High prevalence of xylazine among fentanyl screen-positive urines from hospitalized patients, Philadelphia, 2021 This study created an LC–MS/MS assay to determine the prevalence of xylazine among fentanyl screen-positive urine samples at Thomas Jefferson University Hospital | Among 81 urine samples screened positive for fentanyl, 78% were positive for xylazine | It was concluded by LC–MS/MS that there was a high prevalence of xylazine in fentanyl screen-positive urine samples submitted to the hospital laboratory |
Ehrman-Dupre et al. (2022) [56] | Management of Xylazine Withdrawal in a Hospitalized Patient: A Case Report This case illustrates a potential treatment pathway for xylazine withdrawal in hospitalized patients | The patient was treated with an infusion of the sedative dexmedetomidine in combination with phenobarbital and tizanidine. Her muscle relaxant was later transitioned to clonidine | After four days on this regimen, the patient was no longer experiencing withdrawal symptoms, suggesting that xylazine withdrawal can be pharmacologically managed in an inpatient setting |
Friedman et al. (2022) [21] | Xylazine spreads across the US: A growing component of the increasingly synthetic and polysubstance overdose crisis This study systematically searched for records describing xylazine-present overdose mortality across the US and assessed time trends and overlap with other drugs. They also gathered ethnographic data from people who inject drugs (PWID), investigating their perspective on increasing xylazine prevalence | Among 10 jurisdictions representing all US census regions, the prevalence of xylazine rose from 0.36% of overdose deaths in 2015 to 6.7% in 2020, with the highest deaths observed in Philadelphia. Fentanyl was found in 98% of xylazine-related deaths. PWID stated that xylazine improved the euphoria and prolonged the duration of fentanyl injections, but often left the user over-sedated or with soft tissue wounds | Xylazine is increasingly present in all US census regions in overdose deaths and is significantly linked to illicitly manufactured fentanyl Ethnographic data suggests that xylazine is sought due to its heightened psychoactive effects |
Love et al. (2023) [53] | Opioid overdoses involving xylazine in emergency department patients: a multicenter study This study evaluated ED patients between 2020 and 2021 for clinical outcome differences for patients with and without xylazine exposures | 321 patients were tested, 90 of whom were positive for xylazine. Analysis of positive patient outcomes showed 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 | Patients testing positive for xylazine with illicit opioid overdose showed cardiac arrest, and coma outcomes occurred significantly less |
Choon et al. (2023) [55•] | A case series of accidental xylazine intoxication in humans: Is there a role of naloxone as an antidote? This case report discusses two accidental human injections with xylazine and challenges the efficacy and benefit of naloxone usage in xylazine intoxication | The first patient was treated with oxygen, IV atropine, and IV naloxone and fully recovered within 24 h The second patient was given supportive treatment with oxygen, fluids, atropine, and noradrenaline and fully recovered within 24 h | Similar outcomes were observed in both cases, so the role of naloxone in xylazine toxicity in humans remains uncertain. General management of xylazine intoxication should focus on supportive care including ventilation and hemodynamics |
Johnson et al. (2021) [47] | Increasing presence of xylazine in heroin and/or fentanyl deaths, Philadelphia, Pennsylvania, 2010–2019 This 10-year study describes trends and characteristics of unintentional deaths from heroin and/or fentanyl overdose with xylazine detections occurring in Philadelphia, Pennsylvania | Between 2010 and 2015, xylazine was detected in 2% of unintentional overdose deaths with heroin and/or fentanyl detections, increasing to 11% in 2016, 10% in 2017, 18% in 2018, and 31% in 2019 | Xylazine detections are evident and steadily increasing in Philadelphia, Pennsylvania |
Ayub et al. (2023) [54] | Xylazine in the Opioid Epidemic: A Systematic Review of Case Reports and Clinical Implications This systematic review assessed the impact of xylazine use and overdoses within the context of the opioid epidemic | Intravenous (IV) administration was a common route for xylazine use, with doses ranging from 40 to 4300 mg. The average dose in fatal cases was 1200 mg, compared to 525 mg in non-fatal cases | This paper summarized the complex nature of xylazine use and the urgent need for a comprehensive approach to its detection, management, and harm reduction |
Reed et al. (2023) [52] | Perspective of people in Philadelphia who use fentanyl/heroin adulterated with the animal tranquilizer xylazine; Making a case for xylazine test strips This study transcribed and analyzed interviews with PWID in which participants were questioned about xylazine and hypothetical xylazine test strips | All 13 participants unanimously disliked the addition of xylazine to their drug supply and had safety concerns about xylazine exposure. All were interested in hypothetical xylazine test strips | In the present study, people who use fentanyl/heroin indicated an interest in testing their drug for the presence of xylazine prior to use |