Fentanyl concentrations are typically interpreted in forensic contexts using postmortem and driving under the influence data, both of which have important limitations. This study describes fentanyl and norfentanyl concentrations measured in an acute, clinical setting among patients presenting to the emergency department with a suspected opioid overdose. A prospective observational study was performed utilizing the Toxicology Investigators Consortium (ToxIC) Drug Overdose Toxico-Surveillance (DOTS) Reporting Program enrolling patients ≥ 13 years old from April 2023 to July 2024 following a life-threatening overdose treated at 17 EDs within the United States. Fentanyl and norfentanyl concentrations were determined by liquid chromatography tandem quadrupole mass spectrometry (lower limit of quantification (LLOQ) 1 ng/mL). Fentanyl and norfentanyl concentrations were summarized using descriptive statistics and stratified by time of ED presentation to blood collection. Fentanyl concentrations were also stratified by norfentanyl concentrations. Three hundred and thirty-one patients presented with a clinical presentation consistent with an opioid overdose and were included in the study. Of these, 248 (74.9

OBJECTIVES:Medetomidine is an alpha-2 adrenoreceptor agonist approved only for veterinary sedation and was reported in the US illicit drug supply starting in 2022. Our aim was to determine the prevalence of medetomidine exposure and associated clinical characteristics among emergency department patients presenting with opioid and/or stimulant overdoses. METHODS:The Toxicology Investigators Consortium (ToxIC) Drug Overdose Toxico-Surveillance (DOTS) Reporting Program included 17 US medical centers. Emergency department (ED) patients with acute opioid and/or stimulant overdose were enrolled between April 2023 and September 2024. Blood was obtained for toxicological analysis, and chart reviews and structured patient interviews were conducted. RESULTS:Among 964 cases, medetomidine was detected in 2.8% (n = 27). After adjusting for confounders, medetomidine exposure was associated with an increased odds (odds ratio: 4.03; 95% CI: 1.35, 10.58) of bradycardia (<50 beats per minute) within 24 hours of presentation. Patients with medetomidine exposure had significantly higher rates of BVM (20.5%) than those without medetomidine exposure (3.7%; P=0.03) but did not require more intubation, BiPAP/CPAP, or naloxone than medetomidine-unexposed patients. No differences between medetomidine-exposed and unexposed groups were found for length of stay, critical care unit disposition, hypotension (<50 mmHg), or sedation. No patients completing an interview (n = 24) reported medetomidine use. CONCLUSIONS:Medetomidine exposure among ED patients with overdose was associated with increased bradycardia but not greater sedation, respiratory support, or need for higher level of care. Sentinel toxico-surveillance can identify emerging drug trends not captured through routine clinical data.

Drug overdoses presenting to emergency departments (EDs) remain poorly characterized largely due to limitations resulting from constraints of hospital toxicology testing. This presents significant challenges for forensic and public health communities, as this population of primarily nonfatal overdoses is frequently not included with other data streams (e.g. fatalities, recreational drug markets), producing incomplete national and regional knowledge. To combat this issue, we performed a comprehensive toxicological analysis on patients presenting to EDs with suspected opioid or stimulant overdose. The Toxicology Investigators Consortium (ToxIC) implemented the Drug Toxico-Surveillance Reporting System at 17 healthcare institutions across the United States between April 2023 and September 2024, 995 patients (mortality rate = 1.0%, n = 10) were enrolled, and blood specimens were collected and analyzed at the Center for Forensic Science Research and Education. All specimens underwent blood alcohol analysis, comprehensive screening of over 1,200 xenobiotics, and quantitation for drugs of interest. At least one xenobiotic was detected in 992 specimens. Most frequently observed drugs include fentanyl (n = 713, mean: 8.0 ± 11 ng/mL), methamphetamine (n = 380, mean: 170 ± 210 ng/mL), and cocaine (n = 306, mean: 7.6 ± 15 ng/mL). There were 629 detections of 43 unique novel psychoactive substances (NPS), including potent alpha-2-agonists xylazine (n = 249, mean: 14 ± 29 ng/mL) and medetomidine (n = 31, mean: 1.5 ± 1.8 ng/mL). Regional trends observed include increased prevalence of methamphetamine in the western and central United States, alpha-2-agonists in the eastern United States, and greater NPS diversity in the eastern United States. Traditional opioids and stimulants were generally detected at higher mean concentrations than their more potent NPS counterparts. Quantitative data varies in comparison to literature on postmortem and driving under the influence of drugs cases. This is the first study to analyze blood specimens and provide quantitative data from a large sample of primarily nonfatal opioid/stimulant related overdoses.

IntroductionCottonmouths, also known as water moccasins, are responsible for <10% of the ∼5000 snakebites reported to America's Poison Centers annually. Envenomations are characterized primarily by local findings. Gastrointestinal signs and hematologic abnormalities have been reported. There are currently 2 antivenoms that are approved by the Food and Drug Administration for the treatment of cottonmouth envenomations. The purpose of this study was to describe the clinical features and antivenom use in the treatment of Northern Cottonmouth envenomations in Texas that were reported to the North American Snakebite Registry.MethodsWe reviewed cottonmouth bites reported between January 1, 2013, and December 31, 2024. Data regarding the circumstances, patient demographics, clinical features, treatment, and outcomes were reviewed.ResultsSixty patients, with a mean patient age of 26 y, were included. Females accounted for 20 cases (33.3%). Lower extremity bites accounted for 35 cases (58.3%). Swelling was observed in 56 cases (93.3%). Emesis was reported in 10 cases (16.7%). Two patients (3.3%) experienced diarrhea. Hematologic laboratory abnormalities were present in 10 patients (16.7%). Antivenom was administered in 47 cases (78.3%), including 22 pediatric patients (84.6%). Three patients (6.4%) who received antivenom experienced minor acute hypersensitivity reactions.ConclusionsCottonmouth envenomations are characterized primarily by local tissue injury. Gastrointestinal signs and hematologic toxicity are observed less commonly. Antivenom is often administered for cottonmouth bites and is associated with a low incidence of acute hypersensitivity reactions. There is a trend toward treating pediatric patients more aggressively.

BACKGROUND AND AIMS:Xylazine, an alpha-2 agonist used in veterinary anesthesia, is increasingly detected in the illicit opioid supply but little is known about the patient level factors associated with xylazine in non-fatal opioid overdose. This study aimed to determine the demographic and clinical factors associated with xylazine detection among emergency department (ED) patients with opioid overdose. DESIGN:Observational study. The Toxicology Investigators Consortium (ToxIC) Fentalog Study is a multicenter, prospective cohort of adult patients with suspected opioid overdose. This analysis included patients enrolled from September 2020 to September 2023. SETTING:In this multicenter study, participating sites included 10 institutions across 9 states in 4 regions of the United States (US): Northeast, Southeast, Midwest and West. PARTICIPANTS:Patients were eligible for Fentalog Study inclusion if they were at least 18 years old, had a suspected opioid overdose and had waste blood available for toxicologic analysis. Only patients with qualitative serum detection of illicit opioids and/or xylazine were included in the final cohort. Of 5554 patients screened, 1289 were eligible for Fentalog Study inclusion. MEASUREMENTS:Based on results of liquid chromatography with a quadrupole time-of-flight mass spectrometer (LCQTOF-MS) and/or liquid chromatography with a triple quadrupole mass spectrometer (LC-QQQ-MS), patients were categorized into those with xylazine detected (positive cases) and without xylazine detected (negative controls). To determine clinical variables associated with xylazine detection, the primary outcome of interest was qualitative detection of xylazine on serum sampling by LCQTOF-MS. FINDINGS:Xylazine was detected in 238 patients. Patients with xylazine were primarily male (78%), white (48%), non-Hispanic (82%) and located in the Northeast US (75%). Bradycardia on initial ED vital signs was associated with higher likelihood of xylazine detection (adjusted odds ratio = 2.11, 95% confidence interval = 1.06-4.06). CONCLUSIONS:Xylazine detection among emergency department opioid overdose patients appears to be more prevalent in the Northeast US and bradycardia appears to be a statistically significant clinical predictor.

OBJECTIVES:The rapidly evolving overdose crisis often involves polydrug use. The Toxicology Investigators Consortium (ToxIC) Drug Overdose Toxico-Surveillance (DOTS) Reporting Program aimed to inform the epidemiology of opioid and stimulant overdoses presenting to the emergency department (ED) using structured patient interviews, medical record reviews, and the collection of blood specimens for qualitative analysis and quantitative drug concentrations. MATERIALS AND METHODS:ToxIC implemented DOTS at 17 medical centers in the United States during 2022-2024. ED patients (aged ≥13 y) who presented with a severe or life-threatening opioid and/or stimulant overdose were screened for eligibility and approached for informed consent. The Center for Forensic Science Research and Education conducted analyses using a panel of >1200 substances through liquid chromatography quadrupole time-of-flight mass spectrometry and quantitative measurements using liquid chromatography tandem quadrupole mass spectrometry. We computed descriptive statistics to summarize main outcomes. RESULTS:During the 2-year sentinel surveillance program, 995 patients were included. Seventy percent (n = 694) of patients presented with a clinically suspected opioid overdose, 13.3% (n = 132) with a suspected stimulant overdose, and 17.0% (n = 169) with an undifferentiated overdose. Fentanyl was detected in most (86%; n = 600) patients with an opioid overdose presentation and 35% (n = 46) of patients with a suspected stimulant presentation. The median (range) fentanyl blood concentration in nonfatal overdoses was 4.5 (1.0-140.0) ng/mL. Mortality was 1.0% (n = 10). PRACTICE IMPLICATIONS:The DOTS Reporting Program addressed a gap in public health overdose data by obtaining quantitative blood concentrations and information on the patient's drug use history that are often not captured in traditional surveillance systems. Future work should consider incorporating patient interviews and quantitative concentrations into overdose data collection to elucidate which drug(s) contribute to the overdose.

Clandestine fentanyl manufacturing oftentimes introduces adulterants and contaminants. This article aims to evaluate trends in adulterants from a cohort of patients presenting to the emergency department (ED) with illicit opioid overdose across the United States. The Fentalog Study group is a multicenter toxicology study group which evaluated ED patients with suspected opioid overdose at 10 medical centers across the United States between 21 September 2020 through 5 February 2024. Comprehensive qualitative toxicology testing was performed on residual serum specimens. Study sites were divided into three geographic regions: West (California, Oregon, Colorado), Midwest (Missouri, Michigan), and East (New York, New Jersey, Pennsylvania, Georgia). Illicit opioids were defined as fentanyl and fentanyl analogs, heroin or its metabolites, and/or novel potent opioids such as nitazenes. 1295 patients with confirmed illicit opioid overdose were included. Males accounted for the majority (73.7%) of patients. The median age was 39 (IQR: 31-54) years. Adulterants were detected in 745 (57.5%) patients. Quinine was the most abundantly encountered adulterant (433; 33.4%). Antihistamines were the most frequently detected class of adulterants (19.6%). There were significant differences in adulterants detected across the three time periods, with notable decreases in adulterants from time-period 1 (79.5%) to time-period 3 (41.7%; P < .001). Adulterants were found in 84 (27.0%) of patients that presented to a hospital in the Western United States, compared with 181 (24.3%) in the Midwest, and 480 (64.4%) of patients in the East (P < .001). Patients with concurrent cocaine were more likely having an adulterant present than those without cocaine present (OR 1.23; 95% CI 1.15-1.31). In contrast, patients with illicit opioids and concurrent methamphetamine were less likely to have adulterants present (OR 0.89; 95% CI 0.84-0.95). Adulteration of illicit opioids was more likely in the Eastern United States and for those with concurrent cocaine and opioid exposures.

BACKGROUND:Levamisole is an adulterant commonly associated with cocaine and has remained in the United States illicit drug supply despite a national decline in cocaine use. Levamisole has recently been detected in seized illicit opioid samples, but limited research exists on this drug combination. This study examined the prevalence of laboratory confirmed levamisole exposures among patients with opioid overdose and assessed its association with sociodemographic characteristics along with patterns of co-occurring substance use. METHODS:This secondary data analysis of the Toxicology Investigators Consortium (ToxIC) Fentalog Study examined patients presenting to any of ten participating emergency departments throughout the United States with a suspected opioid overdose between 2020-2024. Chart reviews were conducted, and waste serum samples underwent liquid chromatography quadrupole time-of-flight mass spectroscopy for comprehensive toxicology analysis. This secondary analysis only included patients who had confirmed opioid exposure at the time of overdose. RESULTS:Of 1,678 patients with confirmed opioid use, 225 (13.4%) were levamisole positive. Levamisole was more commonly detected in females (34.2%) compared to males (25.5%, p < 0.01), and there were significant age-related and racial/ethnic differences. Levamisole exposure was associated with a significantly higher number of confirmed co-exposures (levamisole: median = 9 substances, no levamisole: median = 6 substances, p < 0.01). It was also more frequently detected with stimulants (p < 0.01), fentanyl, and fentanyl analogues such as butyrylfentanyl, N-methyl-norfentanyl, ortho-fluorofentanyl, and para-flurorofentanyl (p < 0.05). CONCLUSIONS:More than one in eight patients presenting with an opioid overdose were exposed to levamisole. These findings provide potential new evidence for levamisole adulteration alongside fentanyl and its analogues.

BACKGROUND:Simultaneous exposure to both benzodiazepines and opioids can lead to synergistic respiratory depression, complicating overdose management. Our objective was to report on the detection of prescription and novel benzodiazepine co-exposures among patients treated in emergency departments (EDs) with suspected opioid overdoses. We aimed to describe novel benzodiazepine exposures in this population and to compare the clinical severity of co-exposure to benzodiazepines and opioids versus opioids alone. METHODS:This study utilized data from the Toxicology Investigators Consortium (ToxIC) Fentalog Study, an observational study at 10 ED sites (Sept 2020-Dec 2023). Waste serum samples were analyzed using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) for the presence of over 1200 novel psychoactive substances (NPS), drugs, therapeutics, and metabolites. Analyses included demographics, clinical severity, and outcomes among those with prescription benzodiazepines, novel benzodiazepines, or no benzodiazepines. RESULTS:Among the patients with opioids present (n = 1427), 29.0% of patients had detectable benzodiazepines. 20.5% of patients had detectable prescription benzodiazepines, and 8.5% of patients had detectable novel benzodiazepines. The most commonly detected prescription benzodiazepine was alprazolam (39.3%); the most common novel benzodiazepine was bromazolam (46.3% of novel benzodiazepines). The median age of those with novel benzodiazepines was 34, which was younger than those without benzodiazepines (40) and those with prescription benzodiazepines (41; p = 0.001). Patients without benzodiazepines received naloxone more frequently (p = 0.02), while novel benzodiazepine co-exposure was associated with higher naloxone nonresponse rates (p = 0.03). Patients with novel benzodiazepines (compared to the opioid-only group) had increased odds of requiring mechanical ventilation (aOR: 2.14; 95% CI: 1.07, 4.05) after adjusting for age, gender, race and ethnicity, and the presence of prescription benzodiazepines and/or fentanyl. CONCLUSIONS:Nearly a third of patients with confirmed opioid overdose presenting to the ED also had concomitant benzodiazepine exposures. Those with novel benzodiazepines had significantly higher odds of intubation, suggesting greater severity of overdose.

Awareness of strychnine as an emerging adulterant is extremely important given its unique clinical findings and morbid clinical sequelae. Strychnine was historically utilized as a tonic, laxative, rodenticide, and adulterant in cocaine, heroin, and methamphetamine. This report describes a cluster of patients with acute opioid overdose presenting to an inner-city medical center with strychnine on serum testing. The data for this case series are from the Toxicology Investigator Consortium Fentalog Study, a 2020-2025 study of patients aged ≥18 years evaluated in 10 regionally distinct emergency departments after a suspected opioid overdose. Comprehensive toxicology testing was performed on residual serum samples. Of the 111 cases submitted by all participating sites in January 2023, 4 cases from the Denver, CO site detected strychnine on comprehensive toxicology testing. The total cases from all sites in January 2023 were 921. The presence of strychnine in biological samples of patients utilizing opioids in this report indicates a possible reappearance in its use as an adulterant, warranting further investigation and public preventative health vigilance. Knowledge of local illicit adulterants is crucial for public healthcare providers because it enables them to consider anticipated clinical course and life-saving interventions.

INTRODUCTION:We believe there are certain behaviors that may predispose people to being bitten by a snake. The purpose of this study was to describe cases reported to the North American Snakebite Registry in which the snakebite victim acknowledged multiple lifetime snakebites and to test the hypothesis that male sex, intentional handling of the snake, alcohol consumption, and maintaining snakes in captivity are associated with sustaining multiple snakebites in a lifetime. METHODS:This was a retrospective review of de-identified patient information reported to the snakebite registry between January 1, 2013 and December 31, 2023. Data regarding the circumstances of the snake encounter, patient demographics, previous snakebites, antivenom administration, and clinical outcomes were reviewed. RESULTS:Of the 2,140 snakebites reported during the study period, 94 (4.4%) involved patients with a history of one or more previous snakebites. Males accounted for 80 (85.1%) victims. Sixty-one (64.9%) bites followed intentional interaction with the snake. Alcohol use was reported in 15 (24.6%) of these cases. Captive snakes were responsible for 18 (29.5%) bites. Of the bites that resulted from unintentional snake interaction, alcohol was implicated in three (9.1%) cases. One (3%) bite was from a captive snake. Acute hypersensitivity reactions were observed in six (7.5%) patients who received antivenom. DISCUSSION:Most patients with multiple lifetime snakebites were intentionally interacting with the snake just prior to being bitten. Maintaining snakes in captivity was reported more frequently in patients with previous bites than among the general snakebite population. Although alcohol use was more common among patients who intentionally interacted with snakes, most patients with multiple lifetime snakebites did not report preceding alcohol use. CONCLUSIONS:Male sex, intentionally handling snakes, and maintaining snakes in captivity are more common in patients with multiple lifetime snakebites than those who have experienced only one bite.

BACKGROUND:Management of severe prolongation of the corrected QT interval (QTc) following acute drug overdose presents a challenge to clinicians, as resulting ventricular dysrhythmias are rare but life-threatening. This study aimed to identify which patients with severe QTc prolongation on presentation to the emergency department (ED) after overdose will develop ventricular dysrhythmias, death, cardiac arrest, the need for rhythm control, or extracorporeal membrane oxygenation utilization. METHODS:Secondary analysis of Toxicology Investigators Consortium Core Registry data from 2013 to 2023. We included patients ≥ 13 years old with acute or acute-on-chronic overdose, toxicology consultation in the inpatient or ED setting, and initial ED electrocardiogram QTc ≥ 500 ms. We excluded patients with no or unknown toxicologic exposure, symptoms unlikely or unknown whether related to exposure, or missing data. The primary outcome was ventricular dysrhythmia. Secondary outcomes included death, cardiac arrest, rhythm control, and extracorporeal membrane oxygenation. Independent variables included patient and overdose characteristics, initial QTc and bicarbonate values, clinical findings, and drug exposures. Multivariable logistic regression was performed with ventricular dysrhythmia as the dependent variable to identify potential predictors. Diagnostic test characteristics were calculated for risk factors identified in the regression model. RESULTS:Of 2764 patients screened, 1265 were included. Forty-eight (3.79%) patients developed ventricular dysrhythmias. Bradycardia (aOR 3.12, 95% CI 1.35-6.90), acidosis (aOR 3.02, 95% CI 1.42-6.23), and shock (aOR 4.54, 95% CI 2.07-9.75) were independently associated with ventricular dysrhythmia on regression analysis and were each associated with every secondary outcome. The absence of any of these findings had a negative predictive value of 98.2% (97.2%-98.9%) for developing ventricular dysrhythmia. CONCLUSIONS:In this large international data registry, we identified predictors of ventricular dysrhythmia in patients presenting to the ED after overdose in the setting of severe QTc prolongation.