Synthetic Cannabinoid Exposure in Adolescents Presenting for Emergency Care.

OBJECTIVE: The objective of this study was to characterize the clinical picture and management of synthetic cannabinoid exposure in a cohort of adolescents. METHODS: Using the 45 participating sites of the Toxicology Investigators Consortium Registry, a North American database, we conducted an observational study of a prospectively collected cohort. We identified all adolescent (12-19 years) cases of synthetic cannabinoid exposure who have received medical toxicology consultation between January 2012 and December 2016. Clinical and demographic data were collected including age, sex, circumstances surrounding exposure, coingestants, clinical manifestations, treatment, disposition, and outcome. RESULTS: We identified 75 adolescents who presented to the emergency department with synthetic cannabinoid exposure. Most were male (91%) and between the ages of 16 and 19 (66%). The most common symptoms were neuropsychiatric with 50 adolescents (67%) exhibiting central nervous system (CNS) manifestations. There was no predominant toxidrome, and 9 patients (12%) were mechanically ventilated. Mainstay of treatment was supportive care. No deaths were reported. CONCLUSIONS: Synthetic cannabinoid exposure in adolescents is primarily characterized by CNS manifestations, which are varied and may be life-threatening. Frontline caregivers should maintain a high index of suspicion for synthetic cannabinoids, especially in adolescents who present with unexplained CNS manifestations, as there is no specific toxidrome or confirmatory rapid drug screen to detect them.

Drug Misuse in Adolescents Presenting to the Emergency Department.

OBJECTIVES: Drug misuse is a disturbing, common practice among youth. One in 4 American adolescents reports consuming prescription medications without a clinical indication. We sought to explore current trends of drug misuse in adolescents. METHODS: Using the 37 participating sites of the ToxIC (Toxicology Investigators Consortium) Case Registry, a cross-country surveillance tool, we conducted an observational cohort study of all adolescents (aged 13-18 years) who presented to emergency departments with drug misuse and required a bedside medical toxicology consultation between January 2010 and June 2013. RESULTS: Of 3043 poisonings, 202 (7%) involved drug misuse (139 [69%] were males). Illicit drugs (primarily synthetic cannabinoids and "bath salts") were encountered in 101 (50%), followed by prescription medications (56 [28%]) and over-the-counter (OTC) drugs (51 [25%]). Dextromethorphan was the most commonly misused legal medication (24 [12%]). Polypharmacy exposure was documented in 74 (37%). One hundred sixty-three adolescents (81%) were symptomatic; of these, 81% had central nervous system impairments: psychosis (38%), agitation (30%), coma (26%), myoclonus (11%), and seizures (10%); and 66 (41%) displayed a specific toxidrome, most commonly sedative-hypnotic. Benzodiazepines were the most frequently administered medications (46%). Antidotes were administered to 28% of adolescents, primarily naloxone, physostigmine, N-acetyl-cysteine, and flumazenil. No deaths were recorded. CONCLUSIONS: Adolescents presenting with drug misuse may be exposed to a wide range and combinations of therapeutics or illicit substances and frequently display central nervous system abnormalities, compromising the ability to obtain a reliable history. Frontline clinicians should maintain a high index of suspicion, as routine toxicology screenings fail to detect most contemporary misused legal and designer drugs.

Acute Poisonings from Synthetic Cannabinoids - 50 U.S. Toxicology Investigators Consortium Registry Sites, 2010-2015.

Recent reports suggest that acute intoxications by synthetic cannabinoids are increasing in the United States (1,2). Synthetic cannabinoids, which were research compounds in the 1980s, are now produced overseas; the first shipment recognized to contain synthetic cannabinoids was seized at a U.S. border in 2008 (3). Fifteen synthetic cannabinoids are Schedule I controlled substances (3), but enforcement is hampered by the continual introduction of new chemical compounds (1,3). Studies of synthetic cannabinoids indicate higher cannabinoid receptor binding affinities, effects two to 100 times more potent than Δ(9)-tetrahydrocannabinol (the principal psychoactive constituent of cannabis), noncannabinoid receptor binding, and genotoxicity (4,5). Acute synthetic cannabinoid exposure reportedly causes a range of mild to severe neuropsychiatric, cardiovascular, renal, and other effects (4,6,7); chronic use might lead to psychosis (6,8). During 2010-2015, physicians in the Toxicology Investigators Consortium (ToxIC) treated 456 patients for synthetic cannabinoid intoxications; 277 of the 456 patients reported synthetic cannabinoids as the sole toxicologic agent. Among these 277 patients, the most common clinical signs of intoxication were neurologic (agitation, central nervous system depression/coma, and delirium/toxic psychosis). Relative to all cases logged by 50 different sites in the ToxIC Case Registry, there was a statistically significant association between reporting year and the annual proportion of synthetic cannabinoid cases. In 2015, reported cases of synthetic cannabinoid intoxication increased at several ToxIC sites, corroborating reported upward trends in the numbers of such cases (1,2) and underscoring the need for prevention.

Multiple poisonings with sodium azide at a local restaurant.

BACKGROUND: Sodium azide is a chemical with a mechanism similar to cyanide. There is concern that it could be used as a chemical warfare agent. OBJECTIVES: We report a cluster of poisonings that occurred at a public restaurant and the subsequent investigation that identified iced tea contaminated with sodium azide (NaN3) and hydrazoic acid, as the foodborne vehicle and agents, respectively. CASE REPORT: Five patients became ill within minutes of drinking iced tea at a restaurant. They all presented to the same Emergency Department with similar symptoms, and improved with fluids, antiemetics, and supportive care. A joint investigation by the Dallas County Department of Health and Human Services, the Texas State Health Department, the Dallas County Southwestern Institute of Forensic Sciences, and the medical toxicologists at the University of Texas Southwestern School of Medicine identified iced tea, contaminated with sodium azide (NaN3) and hydrazoic acid, as the foodborne vehicle and agents, respectively. CONCLUSION: The recurrence, and seriousness, of these events suggests a need for continued education of emergency providers. Emergency physicians should consider exposures to toxic chemicals in their differential when a cluster of patients presents with similar symptoms over a short period of time.

Predicting adverse cardiovascular events in emergency department patients with bupropion overdose.

OBJECTIVES: Bupropion toxicity can lead to adverse cardiovascular events (ACVE), but delayed onset of toxicity makes risk stratification difficult. This study aimed to validate previously defined predictors of ACVE and identify novel predictors among patients presenting to the emergency department (ED) after bupropion overdose. METHODS: This secondary analysis of prospective data from the Toxicology Investigators Consortium Core Registry analyzed adult acute or acute-on-chronic bupropion exposures from 2015 to 2018. The primary outcome was ACVE (any of the following: myocardial injury, shock, ventricular dysrhythmia, or cardiac arrest). Potential predictors of ACVE included previously derived predictors in the overall drug overdose population (prior cardiac disease, initial serum bicarbonate < 20 mEq/L, and initial QTc ≥ 500 ms), exposure circumstances, and initial serum lactate value. Candidate predictors were evaluated using univariate analysis and multivariable regression modeling. Receiver operator characteristic curves were used to derive optimal cutoff points for novel predictors, and prognostic test characteristics were calculated. RESULTS: Of 355 patients analyzed, ACVE occurred in 34 (9.6%) patients. Initial serum bicarbonate < 20 mEq/L (adjusted odds ratio [aOR] 4.42, 95% confidence interval [CI] 1.94-10.0) and initial QTc ≥ 500 ms (aOR 2.52, 95% CI 1.01-6.09) independently predicted ACVE. Exposure circumstances did not predict ACVE. Initial serum lactate > 5.2 mmol/L independently predicted ACVE (aOR 12.2, 95% CI 2.50-75.2) and was 90.7% specific with 80.3% negative predictive value. CONCLUSIONS: Metabolic acidosis and QTc prolongation were validated as predictors of ACVE in ED patients with bupropion overdose. Serum lactate elevation was strongly predictive of ACVE in this study and warrants further investigation.

From Patient Registry to Multi-Center Research Consortium: the Toxicology Investigators Consortium (ToxIC) Turns Fifteen.

The Toxicology Investigators Consortium (ToxIC) was launched as a prospective multi-center registry of cases who receive medical toxicology consultations. Now, with over 100,000 cases, the Core Registry continues to address many medical toxicology research questions and has served as the foundation for multiple sub-registries, including the North American Snakebite Registry and the Medications for Opioid Use Disorder sub-registry. ToxIC also has evolved a portfolio of non-registry-based projects utilizing medical toxicology physician site principal investigators who enroll patients through emergency departments, irrespective of whether they received a medical toxicology consultation. These studies include the FDA-ACMT COVID-19 ToxIC Pharmacovigilance Project, which identifies adverse drug reactions related to the treatment of COVID-19, the Fentalog Study a toxico-surveillance study of suspected opioid overdose cases, the Drug Overdose Toxico-Surveillance Reporting Program which enrolls either suspected stimulant or opioid overdose cases, and the just being launched Real-World Examination of Naloxone for Drug Overdose Reversal project. Given ToxIC's experience in multi-center studies and its well-developed infrastructure, it is well-positioned to provide a nimble response on the part of the medical toxicology community to addressing evolving toxicological threats, drug and chemical toxicosurveillance, and other important medical toxicology priorities.

Remdesivir Discontinuation Decisions Based on Thresholds of Aminotransferase in an Observational Registry.

BACKGROUND: Remdesivir is an antiviral approved by the US Food and Drug Administration (FDA) for treatment of coronavirus disease 2019 (COVID-19), and aminotransferase elevation is commonly reported. Thresholds to be considered for discontinuation due to alanine aminotransferase (ALT) elevation differ between the FDA and European Medicines Agency (EMA). The primary objective was to describe aminotransferase thresholds being used in real-world practice for discontinuation of remdesivir in patients with COVID-19, and compare them with labeled recommendations. METHODS: This study used a descriptive design based on an ongoing national registry of adverse events, the FDA ACMT COVID-19 ToxIC (FACT) pharmacovigilance project, with 17 participating health systems in the USA. Cases were identified retrospectively for an 18-month period (23 November 2020-18 May 2022). Classification of discontinuation as premature and due to aminotransferases was based on chart documentation by the treating team. RESULTS: Of 1026 cases in the FACT registry, 116 cases were included with supplemental data forms completed for aminotransferase elevation with remdesivir, defined a priori for inclusion as ALT doubling or increasing by ≥ 50 U/L. ALT was elevated prior to remdesivir in 47% and increased above baseline during dosing by a median of 92 U/L [interquartile range (IQR) 51-164, max 8350]. Remdesivir was discontinued early in 37 (31.9%) patients due to elevated aminotransferases. The ALT threshold for premature discontinuation was median 200 U/L (IQR 145-396, range 92-5743). Among patients with premature discontinuation of remdesivir for aminotransferase elevation, only 21.6% met FDA criteria to consider discontinuation, and 40.5% met prior EMA criteria to consider discontinuation. CONCLUSION: In this descriptive study of real-world practice in the USA, clinicians are overall making more conservative treatment decisions than are recommended for consideration in approved drug labeling of discontinuation, with wide variation in the aminotransferase thresholds being used.

Psychostimulant drug co-ingestion in non-fatal opioid overdose.

Introduction: In 2019, there were over 16,000 deaths from psychostimulant overdose with 53.5% also involving an opioid. Given the substantial mortality stemming from opioid and psychostimulant co-exposure, evaluation of clinical management in this population is critical but remains understudied. This study aims to characterize and compare clinical management and outcomes in emergency department (ED) overdose patients with analytically confirmed exposure to both opioids and psychostimulants with those exposed to opioids alone. Methods: This was a secondary analysis of a prospective consecutive cohort of ED patients age 18+ with opioid overdose at 9 hospital sites from September 21, 2020 to August 17, 2021. Toxicologic analysis was performed using liquid chromatography quadrupole time-of-flight mass spectrometry. Patients were divided into opioid-only (OO) and opioid plus psychostimulants (OS) groups. The primary outcome was total naloxone bolus dose administered. Secondary outcomes included endotracheal intubation, cardiac arrest, troponin elevation, and abnormal presenting vital signs. We employed t-tests, chi-squared analyses and multivariable regression models to compare outcomes between OO and OS groups. Results: Of 378 enrollees with confirmed opioid overdose, 207 (54.8%) had psychostimulants present. OO patients were significantly older (mean 45.2 versus 40.6 years, p < 0.01). OS patients had significantly higher total naloxone requirements (mean total dose 2.79 mg versus 2.12 mg, p = 0.009). There were no significant differences in secondary outcomes. Conclusion: Approximately half of ED patients with confirmed opioid exposures were also positive for psychostimulants. Patients in the OS group required significantly higher naloxone doses, suggesting potential greater overdose severity.

American College of Medical Toxicology Research Agenda 2024-2030.

ACMT recognizes the pivotal role of high-quality research in advancing medical science. As such, the establishment of a formal research agenda for ACMT is a leap forward in communicating the priorities of the College, its members, and the patient populations we serve. This thoughtfully crafted agenda will serve as a strategic compass for ACMT, guiding our pursuit of scientific discovery, fostering innovation, and enhancing outcomes for patients and communities affected by poisonings and exposures.

Factors Affecting the Choice to Specialize in Medical Toxicology.

INTRODUCTION: Medical toxicology is a small but growing specialty. To ensure that the specialty continues to grow and attract strong candidates, it is important to understand what influences physicians to pursue medical toxicology training. This would allow for targeted interventions to recruit strong candidates to the field. METHODS: A cross-sectional survey was sent via email to current medical toxicology fellows and to medical toxicologists who completed fellowship in the last 5 years. ACMT listservs were utilized to target recipients. The survey was created through an iterative writing process among the study authors. Responses to the survey were recorded in REDCap. Descriptive statistics were obtained and analyzed. RESULTS: A total of 126 participants responded to the survey request (46 fellows and 80 recent graduates). Most were primarily trained in emergency medicine. Interest in medical toxicology usually started during residency when exposure to the field was highest. Most respondents cite a mentor as a primary influence in pursuing medical toxicology training. CONCLUSIONS: Among current fellows and recent graduates of medical toxicology, having a mentor in the field of medical toxicology, having exposure to medical toxicology during residency, and participating in a clinical rotation in medical toxicology were common shared experiences that led to the decision to subspecialize in the field. These results may guide targeted intervention to continue to recruit strong candidates to medical toxicology.

Adverse Events in Pregnant Patients Treated with Coronavirus Disease 2019 Therapeutics.

BACKGROUND: Pregnant patients are at high risk of maternal and fetal complications from Coronavirus Disease 2019 (COVID-19) infections. The COVID-19 pandemic prompted a surge in the development and repurposing of therapies for the SARS-CoV-2 virus. Evidence is sparse on the efficacy and safety of these therapies in pregnant patients. Our objective was to describe adverse events (AEs) to COVID-19 therapeutics in pregnant patients. METHODS: This was a case series of AEs reported to the FDA ACMT COVID-19 ToxIC (FACT) Pharmacovigilance Project between November 23, 2020, and June 28, 2022. FACT is an ongoing toxicosurveillance project at 17 sites to proactively identify and report AEs associated with COVID-19 therapeutics. Abstracted information includes demographics, case narratives, exposure details, clinical information, pregnancy details, treatments, and outcomes. RESULTS: Forty-six COVID-19-positive pregnant patients who developed AEs following COVID-19 therapeutics were reported to the FACT Pharmacovigilance Project over 19 months. The most reported medications were remdesivir in 22 patients (47.8%) and casirivimab/imdevimab in 8 patients (17.4%). Four patients (8.7%) had life-threatening clinical manifestation, and 16 patients (34.8%) required intervention to prevent permanent damage. The most common maternal and fetal events were elevated serum alanine aminotransferase (26.1%) and non-reassuring fetal heart patterns (20.0%), respectively. CONCLUSIONS: This case series reports AEs of elevated serum alanine aminotransferase, maternal bradycardia, maternal hypothermia, non-reassuring fetal heart patterns, and emergent or unplanned cesarean sections following administration of several COVID-19 therapeutics. This study was not designed to definitely identify causation, and further study is needed to evaluate the causal role of these therapeutics in AEs affecting pregnant COVID-19 patients.

Characterization of Nonfatal Opioid, Cocaine, Methamphetamine, and Polydrug Exposure and Clinical Presentations Reported to the Toxicology Investigators Consortium Core Registry, January 2010-December 2021.

INTRODUCTION: To characterize and compare opioid-only, cocaine-only, methamphetamine-only, opioid-and-cocaine exposure, and opioid-and-methamphetamine exposure and to examine clinical presentations, leading to a better understanding of overdose effects involving these drug exposures. METHODS: We examined drug exposures in the Toxicology Investigators Consortium (ToxIC) Core Registry from January 2010 to December 2021, a case registry of patients presenting to participating healthcare sites that receive a medical toxicology consultation. Demographic and clinical presentations of opioid-only, cocaine-only, methamphetamine-only, and opioid-and-cocaine exposure, and opioid-and-methamphetamine exposure consultations were described; differences between single and polydrug exposure subgroups were calculated to determine statistical significance. Clinical presentations associated with exposures were evaluated through calculated adjusted relative risk. RESULTS: A total of 3,883 consultations involved opioids, cocaine, methamphetamine, opioid-and-cocaine exposure, or opioid-and-methamphetamine exposure. Opioid-only (n = 2,268, 58.4%) and methamphetamine-only (n = 712, 18.3%) comprised most consultations. There were significant differences in clinical presentations between exposure subgroups. Opioid-and-cocaine exposure consultations were 8.15 times as likely to present with a sympathomimetic toxidrome than opioid-only. Conversely, opioid-and-cocaine exposure and opioid-and-methamphetamine exposure were 0.32 and 0.42 times as likely to present with a sympathomimetic toxidrome compared to cocaine-only and methamphetamine-only consultations, respectively. Opioid-and-cocaine exposure was 0.67 and opioid-and-methamphetamine exposure was 0.74 times as likely to present with respiratory depression compared to opioid-only consultations. Similarly, opioid-and-cocaine exposure was 0.71 and opioid-and-methamphetamine exposure was 0.78 times as likely to present with CNS depression compared to opioid-only consultations. CONCLUSIONS: Used in combination, opioids and stimulants may mask typical clinical presentations of one another, misattributing incorrect drugs to overdose in both clinical treatment and public health surveillance.

Identification of Bradycardia Following Remdesivir Administration Through the US Food and Drug Administration American College of Medical Toxicology COVID-19 Toxic Pharmacovigilance Project.

Importance: The rapid spread and mortality associated with COVID-19 emphasized a need for surveillance system development to identify adverse events (AEs) to emerging therapeutics. Bradycardia is a remdesivir infusion-associated AE listed in the US Food and Drug Administration-approved prescribing information. Objective: To evaluate the magnitude and duration of bradycardic events following remdesivir administration. Design, Setting, and Participants: A multicenter cohort study of patients with recorded heart rate less than 60 beats per minute within 24 hours after administration of a remdesivir dose was conducted between November 23, 2020, and October 31, 2021. Participants included patients hospitalized with COVID-19 at 15 medical centers across the US. Patients excluded had AEs unrelated to bradycardia, AEs in addition to bradycardia, or first onset of bradycardia after 5 remdesivir doses. Exposures: Remdesivir administration. Main Outcomes and Measures: Linear mixed-effect models for the minimum HR before starting remdesivir and within 24 hours of each dose included doses as fixed effects. Baseline covariates were age (≥65 years vs <65 years), sex (male vs female), cardiovascular disease history (yes vs no), and concomitant use of bradycardia-associated medications. The interactions between variables and doses were considered fixed-effects covariates to adjust models. Results: A total of 188 patients were included in the primary analysis and 181 in the secondary analysis. The cohort included 108 men (57.4%); 75 individuals (39.9%) were non-Hispanic White and mean (SD) age was 61.3 (15.4) years. Minimum HR after doses 1 to 5 was lower than before remdesivir. Mean minimum HR was lowest after dose 4, decreasing by -15.2 beats per minute (95% CI, -17.4 to -13.1; P < .001) compared with before remdesivir administration. Mean (SD) minimum HR was 55.6 (10.2) beats per minute across all 5 doses. Of 181 patients included in time-to-event analysis, 91 had their first episode of bradycardia within 23.4 hours (95% CI, 20.1-31.5 hours) and 91 had their lowest HR within 60.7 hours (95% CI, 54.0-68.3 hours). Median time to first bradycardia after starting remdesivir was shorter for patients aged 65 years or older vs those younger than 65 years (18.7 hours; 95% CI, 16.8-23.7 hours vs 31.5 hours; 95% CI, 22.7-39.3 hours; P = .04). Median time to lowest HR was shorter for men vs women (54.2 hours; 95% CI, 47.3-62.0 hours vs 71.0 hours; 95% CI, 59.5-79.6 hours; P = .02). Conclusions and Relevance: In this cohort study, bradycardia occurred during remdesivir infusion and persisted. Given the widespread use of remdesivir, practitioners should be aware of this safety signal.

Clinical Presentations, Treatments, and Outcomes of Non-native Snake Envenomations in the United States Reported in the North American Snakebite Registry.

BACKGROUND: Non-native snake envenomations in the United States are uncommon with much unknown about a patient's presenting signs and symptoms. Antivenoms for non-native snake envenomations are not typically available in hospital pharmacies which may limit their administration. What are the clinical presentations, treatments, and outcomes of non-native snake envenomation cases reported to the North American Snakebite Registry (NASBR) of the Toxicology Investigators Consortium (ToxIC)? METHODS: This is a descriptive review of all non-native envenomations reported to the NASBR from 2013 to March 2022. Data abstracted included snake species, patient history, clinical signs, diagnostics, treatment (including antivenom usage), follow-up, and final outcome. RESULTS: We identified 19 non-native snake envenomations resulting from encounters with eleven different species, eight of which belonged to the Viperidae family. The most common presenting symptoms were edema (18 patients), ecchymosis (seven patients), and necrosis (six patients). Systemic effects and hematologic abnormalities were less common. The most common treatments were extremity elevation and analgesia, with two patients receiving mechanical ventilation. Ten patients received antivenom. No patients died. Three patients had loss of mobility in a digit at the last follow-up visit. One patient had permanent tissue loss of a small area on a finger. CONCLUSIONS: The results of this study suggest that non-native snake envenomations in the United States frequently cause local soft tissue effects and less frequently cause systemic or hematologic effects. Most patients received antivenom, although several patients envenomated by snakes for which a specific antivenom exists did not receive any. Sequelae at the last follow-up of such encounters consisted of local mobility deficits.

Naloxone Use in Novel Potent Opioid and Fentanyl Overdoses in Emergency Department Patients.

Importance: Synthetic opioids, such as the fentanyl analogue and nitazene drug class, are among the fastest growing types of opioids being detected in patients in the emergency department (ED) with illicit opioid overdose (OD). However, clinical outcomes from OD of novel potent opioids (NPOs), specifically nitazenes, are unknown aside from small case series. Objective: To determine naloxone administration and clinical sequelae of patients who were in the ED with NPO overdose compared with fentanyl OD. Design, Setting, and Participants: This is a cohort study subgroup analysis of adults admitted to the ED and tested positive for NPOs among in the ongoing nationwide ToxIC Fentalog cohort study from 2020 to 2022. Patients who were in the ED with a presumed acute opioid OD and residual blood samples were included, and those testing positive for NPOs were analyzed. Patients were included in this analysis if their confirmatory testing was positive for an NPO analyte, such as brorphine, isotonitazene, metonitazene, and/or N-piperidinyl etonitazene. A comparison group included patients that were positive for fentanyl and devoid of any other analytes on toxicologic analysis. Exposures: Patients were exposed to NPOs, including brorphine, isotonitazene, metonitazene and/or N-piperidinyl etonitazene. Main Outcomes and Measures: The primary outcome was the total number of naloxone doses and total cumulative naloxone dose administered as part of routine clinical care following the OD. Naloxone requirements and clinical sequelae of NPO-positive patients were compared with those testing positive for fentanyl only. Results: During the study period, 2298 patients were screened, of whom 717 met inclusion criteria, 537 had complete laboratory testing data, with 11 (2.0%) positive for only fentanyl and 9 (1.7%) positive for NPOs (brorphine, isotonitazene, metonitazene, or N-piperidinyl etonitazene). The age range of patients was aged 20 to 57 years (4 males [44.4%] and 5 females [55.6%]). The NPO group received a statistically significantly higher mean (SD) number of naloxone boluses in-hospital (1.33 [1.50]) compared with the fentanyl group (0.36 [0.92]) (P = .02), which corresponded to a moderately large effect size (Cohen d = 0.78). Metonitazene overdose was associated with cardiac arrest and more naloxone doses overall. Metonitazene cases had a mean (SD) number of 3.0 (0) naloxone doses, and 2 of 2 patients (100%) with metonitazene overdoses were administered cardiopulmonary resuscitation. Conclusions and Relevance: In this cohort study of patients admitted to the ED with confirmed opioid overdose testing positive for NPOs, in-hospital naloxone dosing was high compared with patients who tested positive for fentanyl alone. Further study is warranted to confirm these preliminary associations.

The Toxicology Investigators Consortium 2022 Annual Report.

Since 2010, medical toxicology physicians from the American College of Medical Toxicology (ACMT) Toxicology Investigators Consortium (ToxIC) have provided reports on their in-hospital and clinic patient consultations to a national case registry, known as the ToxIC Core Registry. De-identified patient data entered into the registry includes patient demographics, reason for medical toxicology evaluation, exposure agents, clinical signs and symptoms, treatments and antidotes administered, and mortality. This thirteenth annual report provides data from 7206 patients entered into the Core Registry in 2022 by 35 participating sites comprising 52 distinct healthcare facilities, bringing the total case count to 94,939. Opioid analgesics were the most commonly reported exposure agent class (15.9%), followed by ethanol (14.9%), non-opioid analgesic (12.8%), and antidepressants (8.0%). Opioids were the leading agent of exposure for the first time in 2022 since the Core Registry started. There were 118 fatalities (case fatality rate of 1.6%). Additional descriptive analyses in this annual report were conducted to describe the location of the patient during hospitalization, telemedicine consultations, and addiction medicine treatments.

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

INTRODUCTION: Illicit opioids, consisting largely of fentanyl, novel synthetic opioids, and adulterants, are the primary cause of drug overdose fatality in the United States. Xylazine, an alpha-2 adrenergic agonist and veterinary tranquilizer, is being increasingly detected among decedents following illicit opioid overdose. Clinical outcomes in non-fatal overdose involving xylazine are unexplored. Therefore, among emergency department patients with illicit opioid overdose, we evaluated clinical outcome differences for patients with and without xylazine exposures. METHODS: This multicenter, prospective cohort study enrolled adult patients with opioid overdose who presented to one of nine United States emergency departments between 21 September 2020, and 17 August 2021. Patients with opioid overdose were screened and included if they tested positive for an illicit opioid (heroin, fentanyl, fentanyl analog, or novel synthetic opioid) or xylazine. Patient serum was analyzed via liquid chromatography quadrupole time-of-flight mass spectroscopy to detect current illicit opioids, novel synthetic opioids, xylazine and adulterants. Overdose severity surrogate outcomes were: (a) cardiac arrest requiring cardiopulmonary resuscitation (primary); and (b) coma within 4 h of arrival (secondary). RESULTS: Three hundred and twenty-one patients met inclusion criteria: 90 tested positive for xylazine and 231 were negative. The primary outcome occurred in 37 patients, and the secondary outcome occurred in 111 patients. Using multivariable regression analysis, patients positive for xylazine had significantly lower adjusted odds of cardiac arrest (adjusted OR 0.30, 95% CI 0.10-0.92) and coma (adjusted OR 0.52, 95% CI 0.29-0.94). CONCLUSIONS: In this large multicenter cohort, cardiac arrest and coma in emergency department patients with illicit opioid overdose were significantly less severe in those testing positive for xylazine.

Lipid emulsion therapy during management of the critically-ill poisoned patient: a prospective cohort study.

BACKGROUND: Despite conflicting data, intravenous lipid emulsion has emerged as a potential antidote. The "lipid sink" theory suggests that following intravenous administration of lipid, lipophilic drugs are sequestered in the vascular compartment, thereby reducing their tissue concentrations. This study sought to determine if survival is associated with the intoxicant's degree of lipophilicity. METHODS: We reviewed all cases in the Toxicology Investigators Consortium's lipid sub-registry between May 2012 through December 2018. Information collected included demographics, exposure circumstances, clinical course, management, disposition, and outcome. The primary outcome was survival after lipid emulsion therapy. Survival was stratified by the log of the intoxicant's octanol-water partition coefficient. We also assessed the association between intoxicant lipophilicity and an increase in systolic blood pressure after lipid emulsion administration. RESULTS: We identified 134 patients, including 81 (60.4%) females. The median age was 40 years (interquartile range 21-75). One hundred and eight (80.6%) patients survived, including 45 (33.6%) with cardiac arrest during their intoxication. Eighty-two (61.2%) were hypotensive, and 98 (73.1%) received mechanical ventilation. There was no relationship between survival and the log of the partition coefficient of the intoxicant on linear analysis (P = 0.89) or polynomial model (P = 0.10). Systolic blood pressure increased in both groups. The median (interquartile range) systolic blood pressure before lipid administration was 68 (60-78) mmHg for those intoxicants with a log partition coefficient < 3.6 compared with 89 (76-104) mmHg after lipid administration. Among those drugs with a log partition coefficient > 3.6, the median (interquartile range) was 69 (60-84) mmHg before lipid and 89 (80-96) mmHg after lipid administration. CONCLUSION: Most patients in this cohort survived. Lipophilicity was not correlated with survival or the observed changes in blood pressure. The study did not address the efficacy of lipid emulsion.

Severe outcomes following pediatric cannabis intoxication: a prospective cohort study of an international toxicology surveillance registry.

INTRODUCTION: An increasing number of jurisdictions have legalized recreational cannabis for adult use. The subsequent availability and marketing of recreational cannabis has led to a parallel increase in rates and severity of pediatric cannabis intoxications. We explored predictors of severe outcomes in pediatric patients who presented to the emergency department with cannabis intoxication. METHODS: In this prospective cohort study, we collected data on all pediatric patients (<18 years) who presented with cannabis intoxication from August 2017 through June 2020 to participating sites in the Toxicology Investigators Consortium. In cases that involved polysubstance exposure, patients were included if cannabis was a significant contributing agent. The primary outcome was a composite severe outcome endpoint, defined as an intensive care unit admission or in-hospital death. Covariates included relevant sociodemographic and exposure characteristics. RESULTS: One hundred and thirty-eight pediatric patients (54% males, median age 14.0 years, interquartile range 3.7-16.0) presented to a participating emergency department with cannabis intoxication. Fifty-two patients (38%) were admitted to an intensive care unit, including one patient who died. In the multivariable logistic regression analysis, polysubstance ingestion (adjusted odds ratio = 16.3; 95% confidence interval: 4.6-58.3; P < 0.001)) and cannabis edibles ingestion (adjusted odds ratio = 5.5; 95% confidence interval: 1.9-15.9; P = 0.001) were strong independent predictors of severe outcome. In an age-stratified regression analysis, in children older than >10 years, only polysubstance abuse remained an independent predictor for the severe outcome (adjusted odds ratio 37.1; 95% confidence interval: 6.2-221.2; P < 0.001). As all children 10 years and younger ingested edibles, a dedicated multivariable analysis could not be performed (unadjusted odds ratio 3.3; 95% confidence interval: 1.6-6.7). CONCLUSIONS: Severe outcomes occurred for different reasons and were largely associated with the patient's age. Young children, all of whom were exposed to edibles, were at higher risk of severe outcomes. Teenagers with severe outcomes were frequently involved in polysubstance exposure, while psychosocial factors may have played a role.