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BackgroundXylazine is an increasingly common adulterant in the North American unregulated drug supply that is associated with adverse health outcomes (e.g., skin infections, overdose). However, there are significant knowledge gaps regarding how xylazine was initially identified and how syringe services program (SSP) staff and clients (people who use drugs) responded to its emergence.MethodsFrom June-July 2023, we conducted qualitative interviews with medical (e.g., clinicians) and frontline SSP staff (e.g., outreach workers) and adult clients with a history of injection drug use at a Miami-based SSP. Inductive memos identified emergent codes; thematic analysis involving team consensus established final themes.ResultsFrom interviews with SSP staff (n = 8) and clients (n = 17), xylazine emergence was identified at different times, in various ways. Initially, during summer 2022, clients identified a "tranquilizer-like substance" that worsened sedation and withdrawal and caused wounds. SSP medical staff later identified this adulterant as xylazine by treating new medical cases and through diverse information-sharing networks that included professional societies and news sources; however, frontline SSP staff and clients needed additional educational resources about xylazine and its side effects. With limited guidance on how to reduce harm from xylazine, SSP clients altered their drug consumption routes, reduced drug use, and relied on peers' experiences with the drug supply to protect themselves. Some individuals also reported preferring xylazine-adulterated opioids and increasing their drug use, including the use of stimulants to avoid over sedation.ConclusionsXylazine's emergence characterizes the current era of unprecedented shifts in the unregulated drug supply. We found that xylazine spurred important behavioral changes among people who use drugs (e.g., transitioning from injecting to smoking). Incorporating these experiences into early drug warning surveillance systems and scaling up drug-checking services and safer smoking supply distribution could help mitigate significant health harms caused by xylazine and other emergent adulterants.

AbstractBackgroundMethodsResultsConclusionFatal drug overdoses have involved both xylazine and fentanyl. Xylazine is a non-opioid substance used in veterinary medicine. This study aimed to model changes in fatal xylazine-involved drug overdose deaths from 2019 to 2023 in Connecticut using overdose death data from the Office of the Chief Medical Examiner.Xylazine-involved drug overdose fatality rates were calculated by number of deaths per year per 100,000 population from 2019 to 2023. We used joinpoint regression modeling to evaluate quarterly overdose rates across age, number of drugs, and drug types with a significance level of p < 0.05.From 2019 to 2023, there were 1116 xylazine-involved fatal overdoses with a cumulative rate of 31.3 deaths per 100,000. Xylazine-involved overdose death rates were significantly higher in Hispanic populations compared to both non-Hispanic White and Black populations (p < 0.05). The joinpoint analyses showed that xylazine-fentanyl mortality rates significantly increased by 0.18 per 100,000 per quarter from 2019 to 2022. Xylazine-fentanyl overdoses involving at least 4 or 5 substances significantly increased. Windham, Hartford, New London, and New Haven counties had the highest xylazine-involved death rates.Xylazine-fentanyl deaths increased from 2019 to 2023, and often involved multiple substances (e.g., cocaine, ethanol, benzodiazepines, and oxycodone). Results show Hispanic populations, those aged 35–49, and 50+ experienced high rates of xylazine-fentanyl overdose deaths. Vulnerable populations in Connecticut for special consideration for future intervention and local resource allocation are recommended. [ABSTRACT FROM AUTHOR]

Background: Xylazine is increasingly prevalent in the unregulated opioid supply in the United States. Exposure to this adulterant can lead to significant harm, including prolonged sedation and necrotic wounds. In the absence of literature describing healthcare providers' experiences with treating patients who have been exposed to xylazine, we aimed to explore what gaps must be addressed to improve healthcare education and best practices. Methods: From October 2023 to February 2024, we conducted a sequential explanatory mixed-methods study, with (1) a quantitative survey phase utilizing convenience sampling of healthcare providers treating patients in Connecticut and (2) a qualitative semi-structured interview phase utilizing purposive sampling of providers with experience treating patients with xylazine exposure. Summary statistics from the survey were tabulated; interview transcripts were analyzed using thematic analysis. Results: Seventy-eight eligible healthcare providers participated in our survey. Most participants had heard of xylazine (n = 69, 95.8%) and had some knowledge about this adulterant; however, fewer reported seeing one or more patients exposed to xylazine (n = 46, 59.8%). After sampling from this subgroup, we conducted fifteen in-depth interviews. This qualitative phase revealed five themes: (1) while xylazine is novel and of concern, this is not necessarily exceptional (i.e., there are other emerging issues for patients who use drugs); (2) participants perceived that xylazine was increasingly prevalent in the drug supply, even if they were not necessarily seeing more patients with xylazine-related outcomes (XROs); (3) patients primarily presented with non-XROs, making it difficult to know when conversations about xylazine were appropriate; (4) patients with XROs may experience issues accessing healthcare; (5) providers and their patients are learning together about how to minimize XROs and reduce the sense of helplessness in the face of a novel adulterant. Conclusions: Xylazine-specific education for healthcare providers is currently insufficient. Improving this education, as well as resources (e.g., drug checking technologies) and data (e.g., research on prevention and treatment of XROs), is crucial to improve care for patients who use drugs. [ABSTRACT FROM AUTHOR]

AbstractThe rise in pregnancy-related overdose deaths has been driven by the use of high-potency illicitly-manufactured synthetic opioids including fentanyl. Xylazine, a veterinary sedative, is increasingly noted as a common adulterant in the United States illicit opioid supply. Exposure to the xylazine-fentanyl combination has been associated with severe harms including sedation, necrotic wounds, and symptoms of xylazine withdrawal. Due to limited data that directly addresses the risks of xylazine exposure during human pregnancy, we conducted a narrative review to summarize the available evidence about the clinical implications of xylazine exposure in pregnancy drawing from evidence from animal models, the general adult population, and the authors’ clinical experiences. Because xylazine exposure presents unique risks to pregnant persons, management of xylazine exposure and related clinical sequelae in pregnant persons warrants nuanced clinical management. Further, additional research is critically needed to develop best practice guidelines related to the management of co-occurring xylazine-opioid exposure during pregnancy including harm reduction strategies to reduce exposure risk during pregnancy. [ABSTRACT FROM AUTHOR]

General anesthesia in calves is easier to perform under field conditions, total intravenous anesthesia (TIVA) than using inhalation anesthesia. In the present study, cardiopulmonary function, anesthetic effects, quality of arousal, hematology, and blood biochemistry were assessed during continuous infusion of a combination solution of 0.01% xylazine, 0.001% butorphanol, and 0.2% propofol (XBP) at doses of 6 (G6; 10 μg/kg/min xylazine, 1 μg/kg/min butorphanol, 200 μg/kg/min propofol) and 9 mL/kg/h (G9; 15 μg/kg/min xylazine, 1.5 μg/kg/min butorphanol 300 μg/kg/min propofol). For both groups, five castrated Holstein calves received intravenous injections of xylazine (0.2 mg/kg) and propofol (2 mg/kg), followed by a continuous infusion of XBP for 60 min to maintain anesthesia. Respiratory management consisted of tracheal intubation followed by spontaneous inhalation of pure oxygen. Cardiopulmonary, anesthesia, hematology, and blood biochemistry variables were assessed at rest (baseline) and every 5 or 15 min after the start of the XBP infusion. Quality of arousal was assessed based on the swallowing reflex recovery time from the stop of XBP infusion, and the sternal position time and standing time after atipamezole administration. XBP produced adequate sedation, analgesia, and muscle relaxation in all calves and maintained stable anesthesia for 60 min. As XBP infusion time passed, rectal temperature and heart rate became lower, and mean arterial blood pressure increased. In both groups, hematologic and blood biochemical effects were mild. The quality of arousal was not different, and all calves were standing. The results of the present study suggested that XBP is useful for TIVA in calves. [ABSTRACT FROM AUTHOR]

Xylazine is used in veterinary medicine as a sedative, analgesic, and muscle relaxant. However, in recent decades, it has frequently been detected in illicit drugs. Xylazine poisoning is characterized by depression of the central nervous and cardiovascular systems. Herein, we present a case of a 41-year-old man who not only had severe depression of the central nervous and cardiovascular systems, but also developed hyperpyrexia during the treatment of xylazine poisoning, which led to his death 3 days after poisoning. This case indicates that, in addition to its other effects, xylazine may also cause hyperthermia, which has not yet been reported in humans. [ABSTRACT FROM AUTHOR]

Background: The bedside diagnosis of acute pulmonary edema is challenging. This study evaluated the breath-by-breath information from electrical impedance tomography (EIT), respiratory mechanics and volumetric capnography (VCap) to assess acute pulmonary edema induced by xylazine administration in anesthetized sheep. Objective: To determine the ability and efficiency of each monitoring modality in detecting changes in lung function associated with onset of pulmonary edema. Methods: Twenty healthy ewes were anesthetized, positioned in sternal (prone) recumbency and instrumented. Synchronized recordings of EIT, spirometry and VCap were performed for 60 s prior to start of injection, during xylazine injection over 60 s (0-60 s) and continuously for 1 min (60-120 s) after the end of injection. After visual assessment of the recorded mean variables, statistical analysis was performed using a mixed effect model for repeated measures with Bonferroni's correction for multiple comparisons, to determine at which breath after start of injection the variable was significantly different from baseline. A significant change over time was defined as an adjusted p < 0.05. All statistics were performed using GraphPad Prism 0.1.0. Results: Electrical impedance tomography showed significant changes from baseline in all but two variables. These changes were observed simultaneously during xylazine injection at 48 s and were consistent with development of edema in dependent lung (decreased end-expiratory lung impedance, ventilation in centro-ventral and ventral lung region) and shift of ventilation into non-dependent lung (decreased non-dependent silent spaces and increased center of ventilation ventral to dorsal and increased ventilation in centro-dorsal and dorsal lung region). All changes in lung mechanics also occurred during injection, including decreased dynamic respiratory system compliance and increased peak expiratory flow, peak inspiratory pressure and airway resistance at 48, 54 and 60 s, respectively. Changes in VCap variables were delayed with all occurring after completion of the injection. Conclusion: In this model of pulmonary edema, EIT detected significant and rapid change in all assessed variables of lung function with changes in regional ventilation indicative of pulmonary edema. Volumetric capnography complemented the EIT findings, while respiratory mechanics were not specific to lung edema. Thus, EIT offers the most comprehensive method for pulmonary edema evaluation, including the assessment of ventilation distribution, thereby enhancing diagnostic capabilities. [ABSTRACT FROM AUTHOR]

Xylazine has been increasingly detected in illegally manufactured fentanyl (IMF) products and overdose deaths in the United States; most xylazine-involved overdose deaths involve IMF. A convenience sample of U.S. adults aged =18 years was identified from those evaluated for substance use treatment during July 2022-September 2023. Data were collected using the Addiction Severity Index-Multimedia Version clinical assessment tool. Among 43,947 adults, 6,415 (14.6%) reported IMF or heroin as their primary lifetime substance-use problem; 5,344 (12.2%) reported recent (i.e., past-30-day) IMF or heroin use. Among adults reporting IMF or heroin as their primary lifetime substance-use problem, 817 (12.7%) reported ever using xylazine. Among adults reporting recent IMF or heroin use, 443 (8.3%) reported recent xylazine use. Among adults reporting IMF or heroin use recently or as their primary lifetime substance-use problem, those reporting xylazine use reported a median of two past nonfatal overdoses from any drug compared with a median of one overdose among those who did not report xylazine use; as well, higher percentages of persons who reported xylazine use reported other recent substance use and polysubstance use. Provision of nonjudgmental care and services, including naloxone, wound care, and linkage to and retention of persons in effective substance use treatment, might reduce harms including overdose among persons reporting xylazine use. [ABSTRACT FROM AUTHOR]

Background and aims: Xylazine is a non‐opioid sedative which has spread rapidly throughout the US illicit drug supply. This study aimed to describe the spread of xylazine throughout the UK illicit drug supply. Methods: Xylazine detections in human biological samples were collated from toxicology laboratories operating in the United Kingdom with the date, location, case type, xylazine concentration and co‐detected drugs (with quantifications where performed) detailed, where permitted, by the corresponding coroner. Drug‐testing cases positive for xylazine were collated from the Welsh Emerging Drugs and Identification of Novel Substances (WEDINOS) drug‐testing postal service with the date, location, purchase intent and co‐detected drugs detailed. Drug seizures made by UK law enforcement were communicated by the Office for Health Improvement and Disparities with the date and location detailed. Results: By the end of August 2023, xylazine was detected in 35 cases from throughout toxicology, drug‐testing and drug seizure sources covering England, Scotland and Wales. There were no cases reported from Northern Ireland. Xylazine was detected in biological samples from 16 people. In most cases where full toxicology results were provided, xylazine was detected with heroin and/or a strong opioid (n = nine of 11), but this polydrug use pattern was not evident in all cases (n = two of 11), suggesting a wider circulation of xylazine in the UK illicit drug market beyond heroin supplies. Evidence from WEDINOS supports this claim, as all 14 drug samples (100%) submitted from across the UK contained xylazine; however, in none of these cases was heroin the purchase intent but rather counterfeit prescription medication tablets (n = 11 of 14), tetrahydrocannabinol (THC) vapes (n = two of 14) or white powder (n = one of 14). Additional evidence for the spread of illicit xylazine comes from five drug seizures made by law enforcement. Conclusions: Xylazine has penetrated the UK illicit drug market and is not limited to heroin supplies. [ABSTRACT FROM AUTHOR]

Xylazine exposure is common in some US cities, but a commercial assay for routine laboratory testing for xylazine is not currently available. We evaluated a pre-release version of the ARK Diagnostics immunoassay for qualitative detection of xylazine/4-hydroxyxylazine in urine. Studies were conducted using either the semi-quantitative assay application (A. Roche Cobas 503 analyzer) or the qualitative assay application (B. Beckman Coulter AU480 analyzer). Study specimens consisted of deidentified patient urine samples submitted for routine drugs-of-abuse testing. Measurements of xylazine (X) were performed by LC–MS–MS to obtain X-NEGATIVE (X <10 ng/mL) and X-POSITIVE (X ≥10 ng/mL). The semi-quantitative ARK assay was calibrated with a 10 ng/mL cutoff for ARK-POSITVE. For (A): among 74 X-POSITIVE samples, there was 1 ARK-NEGATIVE result (false-negative rate = 1.4%); among 78 X-NEGATIVE samples by LC–MS–MS, there were 0% ARK-POSITIVE results (false-positive rate = 0%). For (B), among 74 X-POSITIVE samples, there were 0 ARK-NEGATIVE results (false-negative rate = 0%); among 78 X-NEGATIVE samples there was 1 ARK-POSITIVE sample (false-positive rate = 1.3%). Common sources of interferences were investigated without evidence of interference. The ARK xylazine/4-OH-xylazine immunoassay was found to be suitable for routine use in screening patient urine samples for presence of xylazine >10 ng/mL. [ABSTRACT FROM AUTHOR]

Abstract Background Xylazine is an increasingly common adulterant in the North American unregulated drug supply that is associated with adverse health outcomes (e.g., skin infections, overdose). However, there are significant knowledge gaps regarding how xylazine was initially identified and how syringe services program (SSP) staff and clients (people who use drugs) responded to its emergence. Methods From June–July 2023, we conducted qualitative interviews with medical (e.g., clinicians) and frontline SSP staff (e.g., outreach workers) and adult clients with a history of injection drug use at a Miami-based SSP. Inductive memos identified emergent codes; thematic analysis involving team consensus established final themes. Results From interviews with SSP staff (n = 8) and clients (n = 17), xylazine emergence was identified at different times, in various ways. Initially, during summer 2022, clients identified a “tranquilizer-like substance” that worsened sedation and withdrawal and caused wounds. SSP medical staff later identified this adulterant as xylazine by treating new medical cases and through diverse information-sharing networks that included professional societies and news sources; however, frontline SSP staff and clients needed additional educational resources about xylazine and its side effects. With limited guidance on how to reduce harm from xylazine, SSP clients altered their drug consumption routes, reduced drug use, and relied on peers’ experiences with the drug supply to protect themselves. Some individuals also reported preferring xylazine-adulterated opioids and increasing their drug use, including the use of stimulants to avoid over sedation. Conclusions Xylazine’s emergence characterizes the current era of unprecedented shifts in the unregulated drug supply. We found that xylazine spurred important behavioral changes among people who use drugs (e.g., transitioning from injecting to smoking). Incorporating these experiences into early drug warning surveillance systems and scaling up drug-checking services and safer smoking supply distribution could help mitigate significant health harms caused by xylazine and other emergent adulterants.

Abstract Background Xylazine is increasingly prevalent in the unregulated opioid supply in the United States. Exposure to this adulterant can lead to significant harm, including prolonged sedation and necrotic wounds. In the absence of literature describing healthcare providers’ experiences with treating patients who have been exposed to xylazine, we aimed to explore what gaps must be addressed to improve healthcare education and best practices. Methods From October 2023 to February 2024, we conducted a sequential explanatory mixed-methods study, with (1) a quantitative survey phase utilizing convenience sampling of healthcare providers treating patients in Connecticut and (2) a qualitative semi-structured interview phase utilizing purposive sampling of providers with experience treating patients with xylazine exposure. Summary statistics from the survey were tabulated; interview transcripts were analyzed using thematic analysis. Results Seventy-eight eligible healthcare providers participated in our survey. Most participants had heard of xylazine (n = 69, 95.8%) and had some knowledge about this adulterant; however, fewer reported seeing one or more patients exposed to xylazine (n = 46, 59.8%). After sampling from this subgroup, we conducted fifteen in-depth interviews. This qualitative phase revealed five themes: (1) while xylazine is novel and of concern, this is not necessarily exceptional (i.e., there are other emerging issues for patients who use drugs); (2) participants perceived that xylazine was increasingly prevalent in the drug supply, even if they were not necessarily seeing more patients with xylazine-related outcomes (XROs); (3) patients primarily presented with non-XROs, making it difficult to know when conversations about xylazine were appropriate; (4) patients with XROs may experience issues accessing healthcare; (5) providers and their patients are learning together about how to minimize XROs and reduce the sense of helplessness in the face of a novel adulterant. Conclusions Xylazine-specific education for healthcare providers is currently insufficient. Improving this education, as well as resources (e.g., drug checking technologies) and data (e.g., research on prevention and treatment of XROs), is crucial to improve care for patients who use drugs.

This study was undertaken to compare the analgesic effects of lidocaine, xylazine, and medetomidine alone and their combinations with lidocaine in Uda sheep. The sheep (n = 6) were assigned to five different epidural treatment groups using a cross-over design with a wash-out period of one week between the treatment groups. The group (A) received lidocaine at 2.86 mg/kg, the group (B) received xylazine at 0.05 mg/kg, the group (C) received medetomidine at 20 µg/kg, the group (D) received lidocaine-xylazine combination at 2.15 mg/kg and 0.125 mg/kg, respectively, and the group (E) received lidocaine-medetomidine combination at 2.15 mg/kg and 5 µg/kg, respectively. The analgesic effect was evaluated by the needle-prick test method. The onset and duration of analgesia in the mentioned regions were recorded. Ataxic and sedative effects were carefully observed and recorded according to the scoring system. Blood was collected at baseline (0), immediately after onset, and 24 hours post-administration. Results showed that medetomidine treatment produced a highly significant (p < 0.01) earlier onset of action (6–8 min) than the rest of the treatment groups. Medetomidine treatment also produced a significantly (p < 0.001) longer duration of analgesia (190-230 min) than the rest of the treatment groups. Lidocaine alone or in combination with xylazine or medetomidine induced severe ataxia, while xylazine and medetomidine alone or in combination with lidocaine produced mild to moderate sedation. In conclusion, epidural administration of medetomidine, lidocaine-xylazine, and xylazine produced a prolonged, longer duration of analgesia with useful systemic sedation in sheep.

The residues of xylazine and its metabolite in foods of animal origin are dangerous to consumers, but there has been no enzyme-linked immunosorbent assay (ELISA) or ELISA-like method reported to determine them so far. In this study, molecularly imprinted microspheres with xylazine as the template were synthesized, and 2,6-dimethylaniline (the metabolite of xylazine) was used as a hapten to prepare a streptavidinated horseradish peroxidase-labeled conjugate. A direct competitive pseudo-ELISA was developed on a microplate for xylazine and 2,6-dimethylaniline in milk. Because biotinylated horseradish peroxidase was employed to enhance the signal, the limits of detection for xylazine (0.003 ng/mL) and 2,6-dimethylaniline (0.005 ng/mL) were increased by 16.7- and 14-fold, respectively, compared to a horseradish peroxidase-labeled conjugate. Moreover, this material may be reused three times. The analysis of milk samples was consistent with values obtained by liquid chromatography tandem mass spectrometry. This is the first paper reporting a molecularly imprinted polymer-based method for the determination of xylazine and its metabolites in food. [ABSTRACT FROM AUTHOR]

This study compared cardiovascular and respiratory effects of dexmedetomidine and xylazine in total intravenous anesthesia with propofol, ketamine, and lidocaine. Twenty-one female dogs were submitted to ovariohysterectomy, premedicated with acepromazine and anesthetized with propofol at a variable rate. The dogs were intubated and supplemented with 100% oxygen in a circuit without rebreathing gases in spontaneous ventilation. They were divided into three groups (n=21) after induction: control (CON) with ketamine (2 mg/kg + 0.6 mg/kg/h) and lidocaine (2 mg/kg + 3 mg/kg/h), DEX and XIL with the same drugs as CON, associated with dexmedetomidine (2 µg/kg + 1 µg/kg/h) or xylazine (0.2 mg/kg + 0.1 mg/kg/h). Propofol consumption, fentanyl analgesic rescue, and cardiorespiratory and blood gas parameters were evaluated during anesthesia. The DEX group had a lower consumption of propofol (0.16 ± 0.09 mg/kg/min) compared to CON (0.24 ± 0.09 mg/kg/min), both not differing from XIL (0.23 ± 0.09 mg/kg/min). The mean arterial pressure was higher after the initial bolus in DEX (107 ± 8 mmHg) and XIL (96 ± 11 mmHg) compared to the CON group (80 ± 10 mmHg). Higher accumulation of arterial carbon dioxide and a decrease in pH were observed in the CON group. The total number of fentanyl rescues did not differ between DEX (7) and XIL (6) and were lower than CON (16). Therefore, dexmedetomidine and xylazine reduced intraoperative fentanyl consumption compared to ketamine and lidocaine infusion alone. However, only dexmedetomidine promoted lower propofol consumption and higher blood pressure values. [ABSTRACT FROM AUTHOR]

For neonatal pups, parenteral anaesthesia is said to be not reliable as low doses induce no anaesthesia whereas high doses render high mortality rates. In this work we have adapted parenteral anaesthesia procedures approved for pups >7 days of age, to anaesthetize neonatal animals (postnatal days 3–4; P3–P4) for keeping them immobile for a long period. In our first experiment we analysed the behaviour of P3–P4 mouse pups for 70 min after intraperitoneal administration of low (37.5/3.75 mg/kg) or high (50/5) doses of a ketamine/xylazine anaesthetic mixture, both in the low range as compared with dosages employed in adults. Pups became immobile in ≈7 min and remained immobile for ≈45 min, irrespective of the age and dose of anaesthesia, younger pups (P3) being apparently more sensitive to the dosage. In the second experiment, we studied the response of P3 pups to mildly nociceptive stimulations, performed with a 4.0 g von Frey filament applied to the dorsal aspect of their paws. These stimuli elicited reaction in 100% of the cases in non-anaesthetized pups. The results indicate that the high dose significantly reduced responses as compared with the low dose of anaesthesia. With the low dose, <40% of the pups were unresponsive to nociceptive stimulation, whereas the high dose resulted in 50–60% of the animals not responding. Mortality was low irrespective of age or dose, suggesting that doses can be further increased if needed for invasive experimental procedures. [ABSTRACT FROM AUTHOR]

The aim was to study the pharmacokinetics of xylazine as a stable anesthetic in goats. In this study, goats were injected with xylazine at the rate of 0.3 mL·kg-1 intramusculally, and blood samples were collected at 1, 3, 5, 10, 20, 30, 45, 60, 90, 120, 180, and 240 min after administration, respectively. Xylazine was extracted by liquid-liquid extraction and separation method, and blood concentration was determined by high performance liquid chromatography (HPLC). The pharmacokinetic characteristics of xylazine in healthy goats were analyzed by pharmacokinetic software. The results showed that the chromatographic peak time of xylazine chromatography was 9-11 min. The specificity of the method was good. The linear correlation coefficient R² of the standard curve was 0.9982 when the concentration of xylazine was in the range of 10-1x1 000 ng. The pharmacokinetic model of xylazine in goats was a one-chamber model with first-order rate absorption, distribution half-life t1/2Ka was (0.49±0.041) min, elimination half-life t1/2Ke was (23.3±2.5) min, and the peak time (Tp) of the highest concentration was (2.8±0.2) min. The total drug clearance CL/F was (0.00016±0.000016) mg·kg-1·min-1 (ng·mL-1), and the minimum effective blood concentration was 56.6 ng ·mL-1, which was consistent with the clinical anesthetic effect. The results showed that xylazine had the characteristics of rapid absorption, wide distribution, short peak time, slow clearance rate, and long anesthetic time in goats, which could be used as the basic drug for the development of goat complex anesthetic preparation. [ABSTRACT FROM AUTHOR]

Carrying out castration on dogs requires anesthesia to prevent movement and relieve pain during the operation. The aim of this study was to evaluate the effects of administering two combinations of general anesthesia, ketamine-xylazine and ketamine-diazepam on haematological parameters for use in castration procedure in local breed of dogs. The dogs used in this study were six local breed of dogs and were randomly divided in two group with three dogs in each group. Blood sampling from the cephalic antebrachii vein of 1 ml was carried out twice, thirty minutes before surgery and sixty minutes after surgery. The average results of post-operative complete blood tests in dogs given ketamine (10 mg/kg body weight, iv)-xylazine (1 mg/kg body weight, iv) anesthesia, include: total erythrocyte count 5.84 x 106 /µL, haemoglobin 12.27 g/dL, haematocrit 36.7%, and leukocytes 15.4 x 10³ /µL. The average results of post-operative complete blood tests in dogs given ketamine (10 mg/kg body weight, iv)-diazepam (0.2 mg/kg body wight, iv) anesthesia, include: total erythrocyte count 5.98 x 106 /µL, haemoglobin 11.77 g/dL, haematocrit 36.23%, and leukocytes 16.4 x 10³ /µL. Based on the results of statistical analysis using the independent t-test, the number of total erythrocytes, haemoglobin, haematocrit and leukocytes post-operative between the two groups was not significantly different (P>0.05). The use of the combination of ketaminexylazine and ketamine-diazepam during castration did not cause changes in the number of total erythrocytes, haemoglobin, haematocrit and leukocytes. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare the sedative and cardiovascular effects of the combination of xylazine-acepromazine versus xylazine-pregabalin - in horses. Four healthy crossbred horses were included in the study and assigned to two treatments. In treatment I (T1), the animals received xylazine hydrochloride (1.00 mg kg-1) in combination with acepromazine maleate (0.05 mg kg-1) intravenously. In treatment II (T2), the animals received intragastric administration of pregabalin (4.00 mg kg-1) followed by xylazine hydrochloride (1.00 mg kg-1) intravenously after 60 min. Head height above ground (HHAG) and echocardiographic indices were evaluated. In T1, recordings were made 5 minubefore and 5, 15, 30, 60, and 90 minu after drug administration. In T2, recordings were made 5 min before pregabalin, 55 minu after pregabalin administration, and then 5, 15, 30, 60, and 90 min after xylazine hydrochloride acepromazine injection. Analyses of the data showed there were no significant differences regarding HHAG and echocardiographic indices between the two treatments. Intragastric administration of pregabalin prior to xylazine could be considered as an alternative premedication regimen when acepromazine administration is contraindicated or undesirable. [ABSTRACT FROM AUTHOR]

The current study aimed to investigate the effect of xylazine sedation (non-sedated versus sedated conditions) and animal temperament on the fetal and maternal hemodynamics during the late stage of gestation in goats. In addition, it aimed to study the concentrations of cortisol and the echotexture of the placentome. Fourteen goats were assigned into two equal groups (n = 7, each) based on the animal's emotional temperament (calm versus nervous groups). All goats were examined for assessment of the blood flow within the fetal aorta (FA), umbilical artery (UMA), and middle uterine artery (MUA) using color-pulsed Doppler ultrasonography. Goats were exposed to light sedation using the recommended dose of xylazine (0.05 mg/Kg Bw) intramuscularly. Goats in each group were reassessed for the studied parameters after sedation. Blood samples were drawn to determine the concentrations of cortisol. Placentome echotexture pixel intensity (PXI) was evaluated using computer image analysis software. Results revealed the significant impact of the xylazine sedation on the Doppler indices of the blood flow within the measured arteries (FA, UMA, and MUA), the PXI of placentome echotexture, and cortisol concentrations. The emotional temperament of goats had significant effects on the blood flow parameters of the MUA and UMA, concentrations of cortisol, and the PXI of the placentome. The interaction effect (sedation x temperament) was noticed in the measured parameters of the UMA blood flow, fetal heart rate, and cortisol concentrations. In conclusion, xylazine sedation and emotional temperaments induced alterations in the echotexture of the placentomes as well as the hemodynamic parameters of late-stage pregnant goats without affecting the pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Objective Animals Studied Procedures Results Conclusions To evaluate the effects of alfaxalone, medetomidine, and xylazine on intraocular pressure (IOP) in domestic pigeons (Columba livia domestica).Eight 12‐month‐old pigeons (16 eyes).The pigeons were randomly assigned to three treatment groups (10 mg/kg of alfaxalone, 0.2 mg/kg of medetomidine, or 10 mg/kg of xylazine) with a 7‐day washout period. The IOP was measured using a rebound tonometer and calibrated using the formula y = 0.439x + 2.059, where y is the tonometric IOP and x is the actual IOP.All three drugs significantly reduced IOP. Alfaxalone led to the least reduction at 5.2 mm Hg, medetomidine reduced IOP to 12.5 mm Hg, whereas xylazine resulted in the greatest reduction at 15.3 mm Hg. Alfaxalone achieved its maximum IOP reduction in 6 min, whereas medetomidine and xylazine required 95 and 115 min, respectively. Both alpha‐2 agonists, medetomidine, and xylazine, showed a prolonged duration of effect and a greater reduction in IOP than those of alfaxalone. All three medications provided adequate sedation without any discernible adverse effects.The findings revealed the varied effects of these drugs on IOP in pigeons, potentially providing valuable insights that could be useful for broader applications in veterinary medicine. [ABSTRACT FROM AUTHOR]

The study evaluated two different anaesthetic protocols in dogs (n=24) for anaesthetic parameters like dose of anaesthetic agents for induction and maintenance of anaesthesia, quality of sedation, induction, maintenance of anaesthesia and recovery. All the animals were first premedicated with butorphanol @ 0.2 mg/kg b.wt. and xylazine @ 1 mg/kg b.wt., i/m, simultaneously. After 15 min of preanaesthetic medication, induction and maintenance of anaesthesia was achieved by administration of propofol @ 3 mg/kg b.wt., i/v in Group-I (n=12) and tiletamine-zolazepam @ 2 mg/kg b.wt., i/v in Group-II (n=12). Both protocols showed excellent quality of induction and maintenance of anaesthesia in the all animals. Physiological parameters like heart rate, respiration rate, rectal temperature and blood saturation of oxygen altered at different time intervals during the anaesthesia, but remained in normal physiological range. Xylazine and butorphanol preanesthetics showed dose sparing effect on induction and maintenance dose of propofol. Propofol resulted in excellent recovery quality and shorter recovery time compared to tiletamine-zolazepam. [ABSTRACT FROM AUTHOR]

Xylazine has emerged as a primary adulterant in fentanyl, exacerbating the complexity of the opioid crisis. Yet, there is no approved drug that can reverse xylazine's pathophysiology. As a prelude to monoclonal antibodies being assessed as a viable therapeutic, a vaccine inquiry was conducted evaluating the immune response in reversing xylazine induced behavior effects. [ABSTRACT FROM AUTHOR]

Our institution has noted an increase in severe upper - extremity infections within the last 2 years. These patients have required transhumeral amputation. This case series demonstrates some of the catastrophic outcomes of these infections in people who inject drugs, which has been postulated to be related to the addition of xylazine to injectable drugs in our community. The study included patients presenting with severe upper-extremity infections resulting from intravenous drug use and requiring upper-extremity amputation between January 1, 2020 and September 30, 2022 at a single, urban, level 1 trauma center. Patient information and clinical images were collected through retrospective chart review. Eight patients were identified at our institution with extensive necrosis of the skin and soft tissues in the forearm and hand, resulting in exposure of the radius and ulna. None of these patients had viable motor function in the hand and presented with a lack of sensation. All underwent transhumeral amputations, including bilaterally in one case. The patients in this case series self-reported injection of tranquilizer-containing drugs, and xylazine has been reported to be present in 91% of heroin and fentanyl samples in our community. Although more studies are needed to confirm that xylazine is the definitive cause of the extensive tissue necrosis seen in these patients, we have found the severity of these infections to be noteworthy, given the likely expansion of xylazine to drug samples beyond our region. Therapeutic V. [ABSTRACT FROM AUTHOR]

Loco-regional anaesthesia and sedation protocols are becoming more popular in ruminant. This research compared some effects of xylazine or acepromazine in combination with lignocaine-bupivacaine mixture for paravertebral nerve block in goats. Twenty adult, apparently healthy West African Dwarf goats were randomly allocated to two groups (five males and five females each). Each group received either xylazine (0.05 mg/kg) + 2 % lignocaine (2mg/kg) – 0.5 % bupivacaine (0.95 mg/kg) mixture (XLB) or acepromazine (0.05 mg/kg) + lignocaine-bupivacaine mixture (ALB). Clinical parameters were recorded immediately (0 minutes) and at 10-minute intervals for an hour and 24 hours. Venipuncture was carried out via jugular vein for haematology before administration of drug (B0), 30 minutes (B30), 60 minutes (B60) and 24 hours (B24). Data was analyzed using descriptive statistics and presented as mean and standard deviation at a significance level of 0.05. The onset of deep sedation following administration of acepromazine was 31.5 ± 0.97, while it was 2.90 ± 0.57 for xylazine. Acepromazine significantly (P < 0.05) reduced the rectal temperatures (RT) of the goats within the first 20 minutes and significantly reduced the respiratory rates of the goats when compared to xylazine. None of the drugs significantly altered the heart rate of the goats. None of the changes in haematological parameters was statistically significant across the sampling time frame. However, red cell parameters (Packed cell volume, red blood cell count, and haemoglobin concentration) and Lymphocyte count were significantly depressed after XLB administration. All the haematological changes were restored to pre-anaesthetic values after 24hours. This study demonstrates that xylazine can be a beneficial alternative and desirable for emergencies in minor ruminant sedation. [ABSTRACT FROM AUTHOR]

Purpose of Review: The opioid epidemic has been responsible for significant morbidity and mortality in the USA and worldwide. As a result, it is essential to recognize the threat these potent drugs can cause when illicitly used. Specifically, introducing fentanyl as a drug adulterant has been shown to impact overdose rates drastically. In this regard, the Drug Enforcement Agency recently released a public safety alert announcing the new threat of a new adulterant called xylazine. Xylazine is a powerful animal sedative with a different mechanism of action when compared to illicit opioids such as heroin and fentanyl. Xylazine is typically injected intravenously via a syringe, often in combination with multiple other drugs. One of the most common drugs, xylazine, is taken in combination with fentanyl, with users of this drug combination describing xylazine as prolonging the euphoric sensation produced by fentanyl. Recent Findings: Xylazine may cause adverse effects such as bradycardia, brief hypertension followed by hypotension, premature ventricular contractions, ataxia, slurred speech, sedation, and respiratory depression. Much of the recent literature on xylazine use in humans comes from case reports and review articles. Summary: Related to widespread use in veterinary medicine and increasing circulation in illicit drug markets, there is a critical need for public awareness and additional clinical-based studies to further increase understanding of mediated or modulated pharmacological effects of xylazine in humans. Further research is urgently needed to more clearly understand the implications of unregulated xylazine in the illicit drug market, to formulate public health interventions, and to implement harm reduction strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: General anesthesia has several main goals, including pain management and cardiovascular support. In this retrospective study, we compared two anesthetic protocols for general anesthesia with isoflurane in horses undergoing emergency laparotomy. In the first, xylazine was administered followed by an intraoperative infusion of lidocaine. In the latter, medetomidine was used for preoperative sedation and intraoperative infusion. We reviewed medical records and registered intraoperative variables, recovery time and quality, and short-term outcomes. Horses receiving preanesthetic xylazine sedation followed by intraoperative infusion showed more respiratory depression and a higher heart rate at the beginning of the surgery prior to lidocaine infusion and at the end of the surgery after the discontinuation of lidocaine infusion, which may indicate insufficient analgesia during this time. Arterial pressure was better maintained when medetomidine was used. Recovery quality was similar, with a longer time required for horses receiving medetomidine. We can conclude that both protocols are suitable for general anesthesia with isoflurane in horses undergoing emergency laparotomy. Medetomidine provided more efficient analgesia at the beginning and end of surgery with longer recovery times, more suitable for anxious and young horses to prevent self-injury during this phase. (1) The main goals of general anesthesia include pain management and a safe anesthetic protocol for smooth recovery. In this retrospective study, we compared two anesthetic protocols for general anesthesia with isoflurane during emergency laparotomy: sedation with xylazine and the intraoperative infusion of lidocaine (X group) versus medetomidine as a preoperative sedation and intraoperative infusion (M group). (2) The medical records of horses who underwent emergency laparotomies between 2016 and 2023 were reviewed. According to the anesthetic protocol, patients were allocated to the X or M groups. Data about the horse, signalment, history, and anesthetic variables were analyzed. (3) Group X had a significantly higher heart rate (HR), lower respiratory rate (RR) and mean and diastolic arterial pressure (MAP/DAP). A progressive increase in HR and RR was observed in both groups. Group X underwent a decrease in RR and an increase in DAP. In Group M, a decrease in MAP and DAP was observed. Group M exhibited a longer recovery time with similar recovery scores. Both protocols provided safe anesthesia for emergency laparotomy, with minor cardiovascular and respiratory depression. Minor respiratory depression was detected when xylazine was used, while recovery was longer with medetomidine. [ABSTRACT FROM AUTHOR]

Historically, xylazine has been utilized in veterinary medicine for decades as an anesthetic and analgesic sedative to facilitate safe handling, diagnostic testing, and surgical procedures in large animals. Currently, xylazine is an emerging threat to human health. It has been detected in the illicit drug supply chain, often as an adulterant. It has been more commonly added to illicit substances, most notably fentanyl, by drugmakers to enhance drug effect. End users are often unaware of its presence. This is alarming given the large number of xylazine-involved overdose deaths while laboratory detections are deficient and reversal agents are absent. Herein, we present the first documented case of xylazine identified via gas chromatography–tandem mass spectrometry at University of California Davis Health despite a peculiarly mild clinical presentation. We hope to increase awareness of this potentially fatal adulterant that is often missed in evaluation and engender further opportunities to study this ongoing issue. [ABSTRACT FROM AUTHOR]

Non-fatal opioid overdoses are associated with significant morbidity. Hypoxic brain injury caused by opioid-induced respiratory depression is a key mechanism of such morbidity. For example, reports describe an amnestic syndrome in opioid users associated with acute injury to the hippocampus, a brain region that is highly susceptible to hypoxic injury. In our recent study we investigated the effects of non-fatal opioid overdose on the hippocampal volume in a well-characterized sample of opioid use disorder (OUD) patients with a history of overdose (OD) compared to those with no prior overdose (NOD). Using structural magnetic resonance imaging (MRI) and voxel-based morphometry, we observed lower hippocampal volume in patients with a history OD than in the NOD group. These findings support an association between non-fatal opioid overdose and hippocampal injury, which we hypothesize contributes to recently reported cases of OUD related amnestic syndrome. Here we review our study findings and the potential pathophysiological mechanisms underlying the acute and delayed hippocampal injury in nonfatal opioid overdose. We also discuss the implications for the risk of overdose and brain injury with the increased prevalence of fentanyl and xylazine contamination of the illicit opioid supply. Lastly, we highlight considerations for clinical management of the underappreciated neurological injury and cognitive dysfunction in OUD patients. [ABSTRACT FROM AUTHOR]

Thirty horses were randomly divided into three groups and sedated with xylazine (1.1 mg/kg). General anaesthesia was induced with diazepam (0.03 mg/kg) and ketamine (2.5 mg/kg). Partial intravenous anaesthesia was maintained with isoflurane and constant rate infusion (CRI) consisting of xylazine 0.33 mg/kg/h and ketamine 1.5 mg/kg/h (X+K); or, higher dose of xylazine 1.2 mg/kg/h and ketamine 3.6 mg/kg/h (XX+KK); or, medetomidine 3.5 µg/kg/h (MED). Horses in each group breathed spontaneously. Heart rate, respiratory rate, peripheral oxygen saturation, palpebral and corneal reflexes, rescue doses with ketamine, invasive arterial blood pressure, inspired and expired gas compositions were measured. Anaesthesia, surgery, and recoveries were timed, and recovery was scored. The xylazine with ketamine groups showed a higher respiratory rate, a significant decrease in consumption of isoflurane, and a shorter time to standing in comparison with the medetomidine group. Recovery of the lowest quality was observed in group MED and a significantly improved recovery was observed in group X+K. The CRI consisting of xylazine with ketamine was shown to be a suitable alternative to CRI with medetomidine in horses undergoing arthroscopy. [ABSTRACT FROM AUTHOR]

Novel Synthetic Opioids (NSO) are frequently found in postmortem (PM) and human performance (HP) forensic toxicology casework, resulting in impairment and fatal overdoses. Developing a broad NSO method benefits public health, as it can be used to identify trends in potent opioid use to develop risk management programs. This project aimed to design a comprehensive, rapid and routine method for the selective analysis of over 250 novel synthetic opioids in blood and urine. This method rapidly extracted 150 µL of blood or urine via protein precipitation followed by size-exclusion filtration, evaporation and reconstitution. Separation and data acquisition were achieved on a 12 min LC–MS-MS method using an F5 column. Data processing was expedited with a custom built-in query created in-house that automated processing and enhanced quality assurance. Validation according to ASB/ANSI Standard 036 was performed and applicability of the method was assessed using proficiency test and authentic casework samples. Assessed in blood and urine qualitatively were 261 unique analytes including fentanyl analogs (fentalogs), nitazenes and other miscellaneous synthetic opioids. As 59 isomeric target analytes were placed into groups due to co-elution, there were 202 distinct acquired targets or target - groups. To demonstrate applicability, 27 proficiency test blood samples received over an approximate 4-year period were analyzed with 126 expected results assessed comprising 25 unique target analytes. Additionally, 617 fatal accidental overdoses within San Francisco in 2022 were retroactively analyzed by this method with almost 10% of cases containing a new NSO substance(s). Such trends and NSO substances were previously unknown in this community. [ABSTRACT FROM AUTHOR]

The recent rise in xylazine use disorders (XUD) in humans is a significant cause for concern as a comprehensive understanding of its molecular pathology is limited, and hence, the ability to reverse the potential adverse effects is lacking. To address this gap, this study evaluates the dose-dependent impact of xylazine and its interactions with various potential targets to identify an optimal reversal strategy. A trichotomized (Low, medium, and high) dose, volume of distribution, and predicted plasma concentration of xylazine were defined. A detailed analysis of xylazine's network protein targets and their tissue-specific expression was performed using classical pharmacoinformatic tools. Molecular docking was used to assess the drug-target affinities and identify potential reversal agents. The study categorized xylazine plasma concentrations ranging from 5-8 µM, 14-20 µM, and 28-40 µM as low, medium, and high concentrations, respectively. Xylazine displayed a preferential affinity for hydrolases, kinases, transporters, and ion channels. Xylazine's network analysis revealed the following proteins: ABCC9, RET, RAPGEF4, ACHE, TGFBR1, PGR, KCNH2, KCNN2, and TRPM8 as its high-affinity targets. The tissue-specific expression of these high-affinity targets suggested potential adverse effects on various organs, particularly skeletal and smooth muscles and the adrenal gland. The study further explored the potential reversal of xylazine pharmacology using alpha2AR-antagonists and CNS stimulants. Prazosin emerged as the most promising candidate, exhibiting a 200 to 2000-fold superior affinity against all high-affinity targets of xylazine. This study contributes to our understanding of xylazine's molecular mechanisms, which could be relevant to its pharmacological effects in all species, and suggests that prazosin can serve as an effective therapeutic option for mitigating xylazine-induced adverse effects in XUD patients, which warrants clinical investigation. [ABSTRACT FROM AUTHOR]

This study was undertaken to compare the analgesic effects of lidocaine, xylazine, and medetomidine alone and their combinations with lidocaine in Uda sheep. The sheep (n = 6) were assigned to five different epidural treatment groups using a cross-over design with a wash-out period of one week between the treatment groups. The group (A) received lidocaine at 2.86 mg/kg, the group (B) received xylazine at 0.05 mg/kg, the group (C) received medetomidine at 20 µg/kg, the group (D) received lidocaine-xylazine combination at 2.15 mg/kg and 0.125 mg/kg, respectively, and the group (E) received lidocaine-medetomidine combination at 2.15 mg/kg and 5 µg/kg, respectively. The analgesic effect was evaluated by the needle-prick test method. The onset and duration of analgesia in the mentioned regions were recorded. Ataxic and sedative effects were carefully observed and recorded according to the scoring system. Blood was collected at baseline (0), immediately after onset, and 24 hours post-administration. Results showed that medetomidine treatment produced a highly significant (p < 0.01) earlier onset of action (6--8 min) than the rest of the treatment groups. Medetomidine treatment also produced a significantly (p < 0.001) longer duration of analgesia (190-230 min) than the rest of the treatment groups. Lidocaine alone or in combination with xylazine or medetomidine induced severe ataxia, while xylazine and medetomidine alone or in combination with lidocaine produced mild to moderate sedation. In conclusion, epidural administration of medetomidine, lidocaine-xylazine, and xylazine produced a prolonged, longer duration of analgesia with useful systemic sedation in sheep. [ABSTRACT FROM AUTHOR]

BackgroundThe bedside diagnosis of acute pulmonary edema is challenging. This study evaluated the breath-by-breath information from electrical impedance tomography (EIT), respiratory mechanics and volumetric capnography (VCap) to assess acute pulmonary edema induced by xylazine administration in anesthetized sheep.ObjectiveTo determine the ability and efficiency of each monitoring modality in detecting changes in lung function associated with onset of pulmonary edema.MethodsTwenty healthy ewes were anesthetized, positioned in sternal (prone) recumbency and instrumented. Synchronized recordings of EIT, spirometry and VCap were performed for 60 s prior to start of injection, during xylazine injection over 60 s (0–60 s) and continuously for 1 min (60–120 s) after the end of injection. After visual assessment of the recorded mean variables, statistical analysis was performed using a mixed effect model for repeated measures with Bonferroni’s correction for multiple comparisons, to determine at which breath after start of injection the variable was significantly different from baseline. A significant change over time was defined as an adjusted p

The article focuses on the detection of medetomidine, a veterinary anesthetic, among patients evaluated in emergency departments for suspected opioid overdoses across Missouri, Colorado, and Pennsylvania from September 2020 to December 2023. Topics include the increasing presence of medetomidine as an adulterant in illicit drugs, its association with other substances like xylazine and fentanyl, and need for further research on its clinical effects and improved addiction treatment strategies.

The author comments on a study by C. Copeland and colleagues on evidence of xylaxine in the United Kingdom illicit drug market beyond heroine supplies. Topics discussed include lessons from other heroin supply disruptions including a prior Taliban opium ban in 2000 to 2001, examples that may represent evidence of a broader shift toward synthetic drugs replacing agricultural products in Europe, and observation on the widespread barriers to accessing social and health services in North America.

Abstract Background The opioid overdose crisis is one of the worst public health crises ever to face the US and emerging evidence suggests its effects are compounded by the presence of drug adulterants. Here we report our efforts to characterize the adulterants present within the local fentanyl supply of San Diego County, obtained from undifferentiated drug samples seized by local law enforcement over the calendar year 2021. Methods Thirty-two participating local law enforcement agencies across San Diego submitted 4838 unknown individual illicit drug samples (total of 312 kg) to the San Diego County Sheriff’s Department Regional Crime Laboratory for identification. Results Qualitative analysis of these samples via FTIR and GC-MS identified methamphetamine (38.7%), fentanyl (20.8%), diacetylmorphine (heroin) (10.2%), codeine (5.8%) and alprazolam (4.3%) as the most common illicit substances and the presence of 52 unique adulterants. The most common adulterants included 4-methylaminoantipyrine (4-MAAP) (10.9%), mannitol (9%), acetaminophen (8.5%), methamphetamine (4.2%), diacetylmorphine (heroin) (3.6%), tramadol (1.9%), and xylazine (1.7%). Several additional pharmacologically active adulterants and contaminants of interest were also identified. Conclusion This analysis is vital for public health use and harm reduction efforts at the level of the individual consumer. Continued direct surveillance of the drug supply is necessary for the detection of potentially harmful adulterants that may pose serious threats to the public.

Abstract Background Xylazine is an alpha-2 adrenergic receptor agonist that has emerged as a contaminant in the illicit drug supply of fentanyl. Xylazine use may be suspected in naloxone-resistant overdoses and atypical, chronic wounds in people who use drugs (PWUD). This case is unique because it is the first case to our knowledge describing wound care for a xylazine-induced wound with a confirmatory xylazine test strip (XTS) in the setting of a syringe services program (SSP) and in the state of Florida. Case presentation A 43-year-old woman with a past medical history of severe opioid use disorder and stimulant use disorder presented to a student-run clinic at a Miami SSP for wound care. She had multiple ulcerations diffusely over her bilateral forearms with surrounding erythema and warmth. Seven weeks later, she presented to clinic again for wound care because her wounds had progressed. At this visit, a XTS was used to confirm the presence of xylazine in her urine. Wound care management and harm reduction strategies employed at both visits were informed by best clinical judgement due to lack of formal guidelines at the time. Wound outcomes are unknown as the patient has not returned to clinic. Conclusions Many PWUD at highest risk for acute and chronic health consequences of xylazine-adulterated fentanyl do not have access to healthcare outside of low barrier clinics and SSPs due to lack of insurance or mistrust of the traditional healthcare system due to stigma. There is an urgent need for access to XTS for PWUD and clinical practice guidelines for the treatment of xylazine-related wounds in outpatient clinics.

Abstract Background Xylazine is a dangerous veterinary sedative found mainly in illicit fentanyl in the Northeast and Midwest. Its role in the Deep South overdose crisis is not well-characterized. Methods We conducted a retrospective review of autopsy data in Jefferson County, Alabama to identify trends in xylazine prevalence among people who fatally overdosed from June 2019 through June 2023. Results 165 decedents met inclusion criteria. While the first identified xylazine-associated overdose was in June 2019, xylazine has become consistently prevalent since January 2021. All cases of xylazine-associated fatal overdoses were accompanied by fentanyl, and most (75.4%) involved poly-drug stimulant use. The average age was 42.2, and most decedents were white (58.8%) and male (68.5%). Overall, 18.2% of people were unhoused at the time of death. Discussion Xylazine is prevalent in the Deep South. Efforts to promote harm reduction, publicly viewable drug supply trends, and legalization of drug checking and syringe service programs should be prioritized.

Abstract Background Addressing xylazine harms are now a critical harm reduction priority, but relatively little epidemiological information exists to determine prevalence, magnitude, and correlates of xylazine use or related outcomes. Methods We conducted a rapid behavioral survey among people who inject drugs (n = 96) in Baltimore November–December 2022. Using a novel indicator of self-reported presumed xylazine effects, we examined prevalence and sociodemographic correlates of past year presumed xylazine effects and association with overdose and wound-related outcomes. Chi-square and descriptive statistics were used to examine bivariate associations overall and separately for those who reported xylazine by name and by reported fentanyl use frequency. Results Almost two-thirds (61.5%) reported experiencing xylazine effects. There were no differences by socio-demographics, but xylazine effects were more commonly reported among those who reported injecting alone (66% vs 38%%, p

Background: The opioid overdose crisis is one of the worst public health crises ever to face the US and emerging evidence suggests its effects are compounded by the presence of drug adulterants. Here we report our efforts to characterize the adulterants present within the local fentanyl supply of San Diego County, obtained from undifferentiated drug samples seized by local law enforcement over the calendar year 2021. Methods: Thirty-two participating local law enforcement agencies across San Diego submitted 4838 unknown individual illicit drug samples (total of 312 kg) to the San Diego County Sheriff's Department Regional Crime Laboratory for identification. Results: Qualitative analysis of these samples via FTIR and GC-MS identified methamphetamine (38.7%), fentanyl (20.8%), diacetylmorphine (heroin) (10.2%), codeine (5.8%) and alprazolam (4.3%) as the most common illicit substances and the presence of 52 unique adulterants. The most common adulterants included 4-methylaminoantipyrine (4-MAAP) (10.9%), mannitol (9%), acetaminophen (8.5%), methamphetamine (4.2%), diacetylmorphine (heroin) (3.6%), tramadol (1.9%), and xylazine (1.7%). Several additional pharmacologically active adulterants and contaminants of interest were also identified. Conclusion: This analysis is vital for public health use and harm reduction efforts at the level of the individual consumer. Continued direct surveillance of the drug supply is necessary for the detection of potentially harmful adulterants that may pose serious threats to the public. [ABSTRACT FROM AUTHOR]

Background: Xylazine is an alpha-2 adrenergic receptor agonist that has emerged as a contaminant in the illicit drug supply of fentanyl. Xylazine use may be suspected in naloxone-resistant overdoses and atypical, chronic wounds in people who use drugs (PWUD). This case is unique because it is the first case to our knowledge describing wound care for a xylazine-induced wound with a confirmatory xylazine test strip (XTS) in the setting of a syringe services program (SSP) and in the state of Florida. Case presentation: A 43-year-old woman with a past medical history of severe opioid use disorder and stimulant use disorder presented to a student-run clinic at a Miami SSP for wound care. She had multiple ulcerations diffusely over her bilateral forearms with surrounding erythema and warmth. Seven weeks later, she presented to clinic again for wound care because her wounds had progressed. At this visit, a XTS was used to confirm the presence of xylazine in her urine. Wound care management and harm reduction strategies employed at both visits were informed by best clinical judgement due to lack of formal guidelines at the time. Wound outcomes are unknown as the patient has not returned to clinic. Conclusions: Many PWUD at highest risk for acute and chronic health consequences of xylazine-adulterated fentanyl do not have access to healthcare outside of low barrier clinics and SSPs due to lack of insurance or mistrust of the traditional healthcare system due to stigma. There is an urgent need for access to XTS for PWUD and clinical practice guidelines for the treatment of xylazine-related wounds in outpatient clinics. [ABSTRACT FROM AUTHOR]

The administration of the α2-adrenergic receptor agonist clonidine via intracerebroventricular route produces hypotension in pentobarbital-anesthetized rats and pressor responses in conscious normotensive rats. We explored the impact of different anesthetics on the central nervous system-dependent cardiovascular effects of clonidine. Normotensive male Wistar rats with guide cannulas previously implanted in the cerebroventricular system were anesthetized with pentobarbital or ketamine/xylazine and prepared for blood pressure measurement. The animals received intracerebroventricular injections of 10 μg clonidine or 0.6 μg dexmedetomidine, and the effects on the systolic, diastolic, mean arterial pressure, and heart rate were evaluated. The influence of 5 μg yohimbine, a selective α2-adrenergic receptor antagonist, was also assessed. The i.c.v. microinjection of clonidine decreased all three components of systemic arterial pressure and the heart rate of pentobarbital-anesthetized rats. On the other hand, clonidine increased the blood pressure and generated a less intense reduction in the heart rate of ketamine/xylazine-anesthetized rats. The pressor and bradycardic effects of clonidine in ketamine/xylazine-anesthetized animals were reproduced by dexmedetomidine, a more selective α2-adrenergic receptor agonist. Notably, the previous intracerebroventricular injection of yohimbine significantly inhibited the hypertensive effect of clonidine and dexmedetomidine. This study discloses that while normotensive rats anesthetized with pentobarbital show hypotensive responses, the stimulation of α2-adrenergic receptors increases the blood pressure in rats under ketamine/xylazine-induced anesthesia, reproducing the effects seen in conscious normotensive animals. Recognizing the mechanisms involved in these differences may allow us to understand better the final effects of clonidine and other α2-adrenergic receptor agonists in the central nervous system, contributing to the repurposing of these drugs. [ABSTRACT FROM AUTHOR]

The article discusses the emergence of new trends in psychoactive drug abuse, specifically focusing on the combination of fentanyl and xylazine. The author highlights the devastating consequences of drug misuse and emphasizes the need for a comprehensive approach to prevention, treatment, education, and public health initiatives. The article describes the effects of krokodil, a synthetic homemade drug that causes severe tissue damage and has gained attention in the world of substance abuse. The author also discusses the increasing prevalence of fentanyl abuse, particularly in North America, and its role in the opioid crisis. The article explores the atypical signs and symptoms of fentanyl overdose, such as muscle rigidity and dyskinesia, and the challenges in recognizing and treating these cases. Additionally, the author discusses the dangers of xylazine, a non-opioid sedative often combined with fentanyl, and its associated effects on the body. The article concludes by emphasizing the importance of understanding the risks and consequences of substance abuse and the need for personalized and effective interventions. [Extracted from the article]

Background: Xylazine is a dangerous veterinary sedative found mainly in illicit fentanyl in the Northeast and Midwest. Its role in the Deep South overdose crisis is not well-characterized. Methods: We conducted a retrospective review of autopsy data in Jefferson County, Alabama to identify trends in xylazine prevalence among people who fatally overdosed from June 2019 through June 2023. Results: 165 decedents met inclusion criteria. While the first identified xylazine-associated overdose was in June 2019, xylazine has become consistently prevalent since January 2021. All cases of xylazine-associated fatal overdoses were accompanied by fentanyl, and most (75.4%) involved poly-drug stimulant use. The average age was 42.2, and most decedents were white (58.8%) and male (68.5%). Overall, 18.2% of people were unhoused at the time of death. Discussion: Xylazine is prevalent in the Deep South. Efforts to promote harm reduction, publicly viewable drug supply trends, and legalization of drug checking and syringe service programs should be prioritized. [ABSTRACT FROM AUTHOR]

Simple Summary: Surgical anesthetic management during short-term procedures such as sterilization is highly relevant due to the hemodynamic, cardiorespiratory, and autonomic alterations that could be present. In the case of sterilization aimed at free-roaming cats, a drug combination to provide hypnosis, analgesia, and autonomic balance can reduce these anesthetic risks. Cat neutering through trap-neuter-return (TNR) programs is a non-lethal alternative for free-roaming cat population control. This study is an evaluation of anesthesia used in the high-quality, high-volume spay and neuter (HQHVSN) model of a TNR program for free-roaming cats in Seoul, Korea. A combination of tiletamine-zolazepam, ketamine, and xylazine (ZKX) was intramuscularly administered to obtain anesthesia. The evaluation was based on the records of 1261 cats with complete records of the injected volume of anesthetics and times, out of a total of 1361 cats. The study confirmed the safety and efficacy of the ZKX combination administered IM in a TNR program in the HQHVSN model and provided a range of appropriate doses. This will enable TNR programs to be more effective and contribute to a stable free-roaming cat population that can be successfully controlled for welfare. This study was performed to evaluate the anesthetic protocol used in the high-quality, high-volume spay and neuter (HQHVSN) of free-roaming cats in Seoul, Korea from 2017 to 2022. The evaluation was performed on a total of 1261 free-roaming cats, with an average weight of 3.48 ± 1.04 kg. The anesthetic combination tiletamine-zolazepam, ketamine, and xylazine (ZKX) was injected intramuscularly. The actual drug doses administered were tiletamine-zolazepam 5.52 ± 1.70 mg/kg, ketamine 8.94 ± 3.60 mg/kg, and xylazine 1.11 ± 0.34 mg/kg. Additional doses were required in 275 cats out of a total of 1261 (21.8%). Following anesthesia and surgery, 1257 cats (99.7%) were returned to their original locations. Four cats (0.3%) died postoperatively. The mean duration of anesthesia (from ZKX combination to yohimbine administration) was 26 ± 22 min for males and 55 ± 36 min for females, while the time from yohimbine administration to the recovery was 31 ± 22 min for males and 20 ± 17 min for females. The use of ZKX for HQHVSN of free-roaming cats is inexpensive, provides predictable results, can be administered quickly and easily in a small volume, and is associated with a low mortality rate during the first 72 h post-surgery. [ABSTRACT FROM AUTHOR]

OBJECTIVE To determine the time of onset and duration of action of distal paravertebral blocks (DPB) in dairy cattle using lidocaine and lidocaine plus xylazine (LX). ANIMALS 10 healthy adult Holstein cows. METHODS Unilateral DPB were performed in 6 cows at L1, L2, and L4. They received 2 treatments (lidocaine and LX) in a blinded random crossover design. Due to treatment failure, 4 additional cows were enrolled. The lidocaine treatment received 1,800 mg (90 mL) of lidocaine, and treatment LX received 1,784 mg (89.2 mL) of lidocaine and 16 mg (0.8 mL) of xylazine. Anesthesia was assessed by response (rapid movements of the tail, directed movements of the feet, or turning of the head towards the site of the needle pricks) to 6 approximately 1-cm deep needle pricks to the paralumbar fossa with a 22-gauge hypodermic needle. The time of onset, duration of action, maximum sedation score, and average heart rate (HR) were compared between treatments. RESULTS Duration of anesthesia was significantly prolonged after DPB in cows treated with LX (251.6 ± 96.94 minutes) compared to lidocaine (105.8 ± 35.9 minutes; P = .01). Treatment with LX was associated with significantly lower average heart rate (56 ± 3 beats/min) compared to cows treated with lidocaine (59 ± 3 beats/min; P = .045). The LX treatment was associated with mild sedation but was not significant (P = .063). CLINICAL RELEVANCE The addition of xylazine to a lidocaine DPB provides a longer duration of anesthesia, is inexpensive and practical, and can be implemented with ease. [ABSTRACT FROM AUTHOR]

Background: Addressing xylazine harms are now a critical harm reduction priority, but relatively little epidemiological information exists to determine prevalence, magnitude, and correlates of xylazine use or related outcomes. Methods: We conducted a rapid behavioral survey among people who inject drugs (n = 96) in Baltimore November–December 2022. Using a novel indicator of self-reported presumed xylazine effects, we examined prevalence and sociodemographic correlates of past year presumed xylazine effects and association with overdose and wound-related outcomes. Chi-square and descriptive statistics were used to examine bivariate associations overall and separately for those who reported xylazine by name and by reported fentanyl use frequency. Results: Almost two-thirds (61.5%) reported experiencing xylazine effects. There were no differences by socio-demographics, but xylazine effects were more commonly reported among those who reported injecting alone (66% vs 38%%, p < 0.007) and daily fentanyl use (47% vs 24% p < 0.003). Those reporting xylazine exposure was three times as likely to report overdose (32% vs 11%, p < 0.03) and twice as likely to have used naloxone (78% vs 46%, p < 0.003). They also more commonly reported knowing someone who died of an overdose (92% vs 76%, p < 0.09) and to report an abscess requiring medical attention (36% vs 19%, p < 0.80). These associations were higher among respondents who specifically named xylazine and those who used fentanyl more frequently, but fentanyl frequency did not fully explain the heightened associations with xylazine effects. Conclusions: This study provides insight into the scope of xylazine exposure and associated health concerns among community-based PWID and suggests measures that may be instrumental for urgently needed research. [ABSTRACT FROM AUTHOR]

Background People who inject drugs (PWID) are at high risk of severe wounds, invasive infections, and overdoses. To date, there are few data on the bacterial and chemical contaminants PWID are exposed to when using illicitly manufactured fentanyls and stimulants. Methods Previously used injection drug use equipment was recovered in St Louis, Missouri, by harm reduction organizations over a 12-month period. Syringe residue was analyzed for bacterial contaminants by routine culturing followed by whole genome sequencing of single bacterial isolates. Chemical adulterants in syringe residue were identified by liquid chromatography–mass spectrometry. Results Bacteria were cultured from 58.75% of 160 syringes analyzed. Polymicrobial growth was common and was observed in 23.75% of samples. Bacillus cereus was the most common pathogen present and was observed in 20.6% of syringe residues, followed closely by Staphylococcus aureus at 18.8%. One hundred syringes underwent mass spectrometry, which demonstrated that chemical adulterants were common and included caffeine, diphenhydramine, lidocaine, quinine, and xylazine. Conclusions Analysis of syringe residue from discarded drug use equipment demonstrates both chemical and biological contaminants, including medically important pathogens and adulterants. [ABSTRACT FROM AUTHOR]