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Xylazine is not a controlled substance; it is marketed as a veterinary drug and used as a sedative, analgesic and muscle relaxant. In humans, it could cause central nervous system depression, respiratory depression, bradycardia, hypotension, and even death. There have been publications of 43 cases of xylazine intoxication in humans, in which 21 (49%) were non-fatal scenarios and 22 (51%) resulted in fatalities. Most of the non-fatal cases required medical intervention. Over recent years xylazine has emerged as an adulterant in recreational drugs, such as heroin or speedball (a cocaine and heroin mixture). From the 43 reported cases, 17 (40%) were associated with the use of xylazine as an adulterant of drugs of abuse. Its chronic use is reported to be associated with physical deterioration and skin ulceration. Literature shows some similar pharmacologic effects between xylazine and heroin in humans. These similar pharmacologic effects may create synergistic toxic effects in humans. Therefore, fatalities among drug users may increase due to the use of xylazine as an adulterant. Xylazine alone has proven harmful to humans and even more when it is combined with drugs of abuse. A comprehensive review of the literature of non-fatal and fatal xylazine intoxication cases including those in which the substance was used as adulterant is presented, in order to increase the awareness in the forensic community, law enforcement, and public health agencies.

Drug-Induced Oxidative HemolysisA 57-year-old woman presented with a 3-day history of shortness of breath and dizziness. Laboratory studies showed severe anemia with hemolysis, along with cellular abnormalities in peripheral blood.

BackgroundXylazine, a veterinary sedative and analgesic, has emerged as a novel adulterant in the US illicit drug supply, frequently co-occurring with fentanyl. This study examines trends in fentanyl-xylazine overdose death rates from 2018 to 2023.MethodsThis serial cross-sectional study examined death certificates from the CDC WONDER database to identify International Classification of Diseases, 10th Revision codes for overdose deaths likely coinvolving fentanyl (T40.4) and xylazine (T42.7 or T46.5). Crude mortality rates per 100 000 were calculated overall and by sex, race/ethnicity, US Census Divisions and state to examine demographic and geographical trends.ResultsFentanyl-xylazine deaths increased from 99 in 2018 to 6020 in 2023. Crude mortality rates rose from 0.03 (95% CI 0.02 to 0.04) to 1.80 (95% CI 1.75 to 1.84) per 100 000. In 2023, rates were higher among males than females (2.63 (95% CI 2.55 to 2.71) vs 0.99 (95% CI 0.93 to 1.03) per 100 000), and higher among black than white individuals (3.21 (95% CI 3.04 to 3.38) vs 1.86 (95% CI 1.80 to 1.92) per 100 000). The Middle Atlantic and New England Census Divisions had the highest regional rates at 5.72 (95% CI 5.49 to 5.95) and 4.32 (95% CI 3.99 to 4.65) per 100 000, respectively.Discussion and conclusionsThe sharp increase in fentanyl-xylazine deaths, particularly among black individuals, highlights both the growing infiltration of xylazine into the illicit drug supply and persistent structural disparities in addiction treatment. Addressing this escalating epidemic requires routine toxicological testing for xylazine and expanded access to trauma-informed care, harm reduction services and interventions such as naloxone, opioid agonist therapies and wound care.

The Z-drugs zolpidem, zopiclone, and zaleplon were hailed as the innovative hypnotics of the new millennium, an improvement to traditional benzodiazepines in the management of insomnia. Increasing reports of adverse events including bizarre behavior and falls in the elderly have prompted calls for caution and regulation. Z-drugs have significant hypnotic effects by reducing sleep latency and improving sleep quality, though duration of sleep may not be significantly increased. Z-drugs exert their effects through increased γ-aminobutyric acid (GABA) transmission at the same GABA-type A receptor as benzodiazepines. Their pharmacokinetics approach those of the ideal hypnotic with rapid onset within 30 min and short half-life (1–7 h). Zopiclone with the longest duration of action has the greatest residual effect, similar to short-acting benzodiazepines. Neuropsychiatric adverse events have been reported with zolpidem including hallucinations, amnesia, and parasomnia. Poisoning with Z-drugs involves predominantly sedation and coma with supportive management being adequate in the majority. Flumazenil has been reported to reverse sedation from all three Z-drugs. Deaths from Z-drugs are rare and more likely to occur with polydrug overdose. Z-drugs can be detected in blood, urine, oral fluid, and postmortem specimens, predominantly with liquid chromatography–mass spectrometry techniques. Zolpidem and zaleplon exhibit significant postmortem redistribution. Zaleplon with its ultra-short half-life has been detected in few clinical or forensic cases possibly due to assay unavailability, low frequency of use, and short window of detection. Though Z-drugs have improved pharmacokinetic profiles, their adverse effects, neuropsychiatric sequelae, and incidence of poisoning and death may prove to be similar to older hypnotics.

To develop and evaluate a predictive model for intensive care unit (ICU) admission among patients with acute sedative-hypnotic overdose. We conducted a retrospective analysis of patients admitted to the emergency department of West China Hospital, Sichuan University, between October 11, 2009, and December 31, 2023. Patients were divided into ICU and non-ICU groups based on admission criteria including the need for blood purification therapy, organ support therapy (ventilatory support, vasoactive drugs, renal replacement therapy, artificial liver), or post-cardiopulmonary resuscitation. Patients were randomly split into a training set and a validation set in a 7:3 ratio. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to optimize variables, followed by a multivariate logistic regression analysis to identify independent risk factors for ICU admission. A nomogram model was constructed and assessed using receiver operating characteristic (ROC) curves, calibration curves, Decision Curve Analysis (DCA), and Clinical Impact Curve (CIC). Predictors in the nomogram included barbiturate overdose, Glasgow Coma Scale (GCS) score, and anion gap at admission. The nomogram demonstrated strong predictive performance with an area under the curve (AUC) of 0.858 (95% CI: 0.788–0.927) in the training set and 0.845 (95% CI: 0.757–0.933) in the validation set. Calibration curves showed the model closely matched the ideal curve, and DCA and CIC indicated high clinical applicability and utility. Barbiturate overdose, initial decreased GCS score and decreased anion gap were identified as independent risk factors for ICU admission in acute sedative-hypnotic overdose. The nomogram model based on these indicators demonstrates good predictive accuracy, discrimination, and clinical utility.

Etomidate is a nonbarbiturate sedative derived from imidazole. Prolonged and excessive use of etomidate can lead to the suppression of adrenocortical function, myoclonus, and even death. This report describes a rare case of a 47-year-old man who died from acute intoxication after oral ingestion of liquid containing etomidate. The cause of death was conclusively attributed to etomidate based on a comprehensive investigation, including autopsy, histopathological examination, toxicological analysis, and biochemical analysis. This is the first reported case of a fatality solely resulting from the oral ingestion of etomidate, which can provide valuable insights for future forensic investigations involving etomidate poisoning. Therefore, it is imperative to share this case with the scientific community.

This paper explores the rapid emergence of xylazine exposure in the USA and its implications for anesthesiologists. Xylazine, a non-opioid sedative and analgesic often used in veterinary medicine, has increasingly been found as an adulterant in the illicit substance supply, leading to serious health implications. The pharmacological properties of xylazine, its clinical effects, and the challenges it poses for clinicans will be discussed. Perioperative strategies for anesthesiologists to manage these potential cases are provided. Furthermore, this paper necessitates an epidemiological understanding for detection and multidisciplinary collaboration in addressing this emerging public health threat. The manuscript concludes by emphasizing the role anesthesiologists will have to play in managing the clinical implications of xylazine and contributing to public health strategies aimed at curbing its misuse.

The number of Americans dying from drug overdoses has risen rapidly, but the contribution of nonopioid drugs to this growth is not well understood. Using vital statistics data from the universe of deaths among US residents in the period 1999-2016, I calculated levels of and increases in overall nonopioid fatal overdose rates and those for subgroups stratified by manner of death, sex, race/ethnicity, and age. Mortality rates were also calculated separately for sedatives, stimulants, antidepressants, and cocaine. Recently developed methods were used to correct for the incomplete reporting of drug involvement on death certificates. From 1999 to 2016 the number of nonopioid drug deaths rose 274 percent, and deaths per 100,000 population rose by 223 percent. Over the same period, opioid-involved fatality counts and rates grew by 371 percent and 307 percent, respectively. Fatal overdose rates involving stimulants increased more than tenfold, with slower growth but higher rates for deaths involving sedatives and cocaine. Midlife non-Hispanic whites generally experienced the highest levels and rise in nonopioid death rates, but cocaine fatality rates were particularly common among nonwhite or Hispanic males ages 40-59. Policies designed to curb the opioid epidemic are probably helpful in reducing nonopioid deaths, but targeted interventions may also be needed.

BackgroundIn 2020, Maryland had the fourth-highest opioid overdose mortality rate in the USA. We describe substances identified in postmortem toxicology screening and designated as cause of death (COD) for overdose decedents in Maryland, including specific combinations of substances designated as COD.MethodsWe performed a retrospective analysis of N=5442 adult overdose decedents (ie, manner of death unintentional or undetermined) in Maryland between January 2020 and December 2021. Overdose mortality data from the State Unintentional Drug Overdose Reporting System. Substances were categorised into five major categories: opioids, alcohol, psychostimulants, sedative-hypnotics and psychotropic drugs. Opioids were further divided into prescription opioids (eg, oxycodone, methadone, tramadol) and illicit opioids (eg, illicitly manufactured fentanyl (IMF), heroin).ResultsOpioids were present in 93% of cases and designated as COD for 92%. IMF was the predominant opioid designated as COD (82% of cases), whereas heroin was COD in only 3%. Psychostimulants, predominantly cocaine, were present in 48% of cases and designated as COD in 41%. Opioids alone were COD in 39% of cases, opioids and psychostimulants in combination were COD for 27%, followed by opioids and alcohol (9%), opioids, alcohol and psychostimulants (6%), and opioids and sedative-hypnotics (4%).ConclusionsIMF is, by far, the leading cause of overdose in Maryland. For more than one-quarter of decedents, opioids and psychostimulants in combination were COD. Specific drug combinations have implications for public health surveillance and harm reduction efforts to keep people who use drugs safer from a volatile drug market and potential fatal overdose.

Background Recent prescribing practices have shifted from benzodiazepines (BZs) toward non‐GABAergic hypnotics, including dual orexin receptor antagonists (DORAs) and melatonin receptor agonists (MRAs). We examined whether hypnotics involved in suicide attempts changed over time in a context‐dependent manner. Methods We conducted a multicenter retrospective cohort study of consecutive patients presenting with suicide attempts at three hospitals in Japan between April 2020 and March 2025. Hypnotics involved in attempts were identified from empty medication packages collected at presentation. Annual proportions of BZs and non‐GABAergic hypnotics (OMs: DORAs and MRAs) were analyzed using Cochran–Armitage trend tests under three conditions: (1) all suicide attempts, (2) overdose‐related attempts, and (3) overdose‐related attempts involving a hypnotic. Additional analyses separated DORAs from MRAs. Results Among 1111 suicide attempt encounters, 648 were overdose‐related. OM involvement increased significantly over time across all denominators. In contrast, BZ involvement declined significantly only among overdose‐related attempts. When OMs were disaggregated, DORA involvement showed a significant upward trend using overdose‐related attempts as the denominator (χ2 = 7.3048, p = 0.006877) and using all suicide attempts as the denominator (χ2 = 7.6384, p = 0.005714). MRA (ramelteon) involvement did not show significant temporal change in either analysis. Overall, the increase in OM involvement was primarily attributable to DORAs. Conclusion Hypnotics involved in suicide attempts changed in a context‐dependent manner during the study period. The increase in non‐GABAergic hypnotics was driven by DORAs, whereas reductions in BZ involvement were detectable only in overdose‐related contexts. These findings suggest that evolving hypnotic availability may influence the profile of medications involved in self‐poisoning. Temporal changes in hypnotics involved in suicide attempts showed context‐dependent shifts. Dual orexin receptor antagonists increased significantly, while benzodiazepine involvement declined only in overdose‐related attempts. Melatonin receptor agonists showed no significant trend during 2020.