Compartment Syndrome after Crotalid Envenomation in the United States: A Review of the North American Snakebite Registry from 2013 to 2021 on Behalf of the ToxIC Snakebite Study Group.

INTRODUCTION: Compartment syndrome (CS) is a rare but serious complication after crotalid envenomation in the United States. Few data are available regarding the epidemiology and management of these cases. Significant controversy and misunderstanding over best practices, including measurement of compartment pressures and use of fasciotomy, exist for this syndrome. This study aims to describe presentation and management of suspected CS cases after native snakebite reported to the North American Snakebite Registry (NASBR). METHODS: This is an analysis of snakebite cases reported to the Toxicology Investigators Consortium NASBR between January 1, 2013 and December 31, 2021. Cases of native snakebite with documented concern for CS were included. RESULTS: Over an 8-y period, 22 cases of suspected CS were identified, representing 1% of all cases reported to the NASBR. Fasciotomies were performed in 41% (n=9) of these cases, most commonly to the upper extremity (67%, n=6). In cases of suspected CS, intracompartmental pressures (ICPs) were rarely measured (23%, n=5) and fasciotomies were performed without measurement of ICPs frequently (56%, n=5). In 1 case, ICPs were measured and found to be low (8 mm Hg) and fasciotomy was avoided. CONCLUSIONS: Measurement of compartment pressures in cases of suspected CS was uncommon in cases reported to the NASBR. Fasciotomy was commonly performed without measurement of compartment pressures.

Oral ulcers in a finger-sucking child after cutaneous wart therapy.

Common skin warts frequently appear on the fingers of children, a patient population in whom finger-sucking is a prevalent habit. Despite overlap between these two pediatric conditions, there are no well-reported specific precautions against the use of topical blistering wart treatments, such as trichloroacetic acid and cantharidin, in finger-sucking children with warts. We report the case of oral ulcers in a pediatric patient secondary to thumb-sucking after receiving treatment for multiple finger warts with combination cryotherapy, trichloroacetic acid, and cantharidin.

Severe E-Cigarette, or Vaping, Product Use Associated Lung Injury Requiring Venovenous Extracorporeal Membrane Oxygenation.

OBJECTIVES: To report a severe case of e-cigarette or vaping product use-associated lung injury with complex course requiring venovenous extracorporeal membrane oxygenation. DESIGN: Case report. SETTING: PICU in an academic medical center. PATIENTS: A 16-year-old girl presenting with gastrointestinal and respiratory symptoms was admitted to our PICU after having progressive respiratory failure and bilateral pulmonary ground-glass opacities on chest CT. INTERVENTIONS: Venovenous extracorporeal membrane oxygenation MEASUREMENTS AND MAIN RESULTS:: After extensive infectious workup was unrevealing, she reported a history of vaping e-cigarette containing either nicotine or delta-9-tetrahydrocannabinol oil prior to symptom onset. She was given a presumptive diagnosis of e-cigarette or vaping product use-associated lung injury. The PICU team in consultation with pulmonology and medical toxicology started high-dose IV methylprednisolone 1 mg/kg bid. Despite initial improvements, she continued to require positive pressure ventilation and developed pneumomediastinum with progression to tension pneumothoraces and a persistent air leak. Unable to maintain her oxygenation, she was placed on venovenous extracorporeal membrane oxygenation for a prolonged course and had a tracheostomy placement. The clinical course, severity, and range of interventions in affected patients around the country have varied widely. Respiratory symptoms have been the most severe, but the constellation of symptoms in e-cigarette or vaping product use-associated lung injury include constitutional symptoms (fevers, weight-loss) and gastrointestinal symptoms (nausea, vomiting, diarrhea). In many cases, steroid use led to rapid clinical improvements. However, other cases with severe illness, like our patient, necessitated high-dose IV steroids, intubation, and venovenous extracorporeal membrane oxygenation. The underlying etiology and pathophysiology of e-cigarette or vaping product use-associated lung injury remains unknown. The Centers for Disease Control and Prevention in conjunction with state/local health departments and the Food and Drug Administration is actively investigating the outbreak. CONCLUSIONS: Clinicians need to be aware of the current outbreak of e-cigarette or vaping product use-associated lung injury and ask about vaping in patients presenting with gastrointestinal and respiratory symptoms. Treatment options are anecdotal and necessitate a multidisciplinary approach.

Treatment of Headache in the Emergency Department: Haloperidol in the Acute Setting (THE-HA Study): A Randomized Clinical Trial.

BACKGROUND: Headache is a common complaint of emergency department (ED) patients and current treatment varies with significant limitations. OBJECTIVE: Our aim was to evaluate the efficacy and safety of 2.5 mg i.v. haloperidol in the treatment of severe benign headache in the ED. METHODS: A randomized, double-blind, placebo-controlled trial was performed in the ED of a single high-volume teaching hospital. Convenience sampling identified 287 eligible patients 13 to 55 years old with benign headache. One hundred and eighteen patients were enrolled to receive either 2.5 mg of haloperidol i.v. or placebo. The primary outcome measure was pain reduction at 60 min. Patients were evaluated for adverse events and follow-up was conducted after discharge. QT measurement was performed at baseline and discharge. RESULTS: Fifty-eight patients received haloperidol and 60 patients received placebo. Patients in the haloperidol group reported an average 4.77-unit reduction in visual analogue scale score at 60 min compared to a 1.87-unit reduction in the control group. Thirty-four patients (58.6%) in the haloperidol group had complete resolution of their headache. Treatment with rescue ketorolac was required in 78.3% of the control group and 31% of the haloperidol group. Adverse events were uncommon, benign, and easily treated. No patients in the haloperidol group were found to have QT lengthening. CONCLUSIONS: This study suggests that 2.5 mg i.v. haloperidol is a rapid and effective treatment for acute, severe, benign headache in ED patients aged 18 to 55 years. Further study is warranted to confirm these results in adolescents. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02747511.

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.

Delta-8-Tetrahydrocannabinol Exposure and Confirmation in Four Pediatric Patients.

INTRODUCTION: Delta-8-tetrahydrocannabinol (THC) is a known isomer of delta-9-THC, both found naturally in the Cannabis sativa plant and thought to have similar potency. Delta-8-THC products are widely accessible in retail shops which may lead to a rise in pediatric exposures with substantial clinical effects. CASE REPORT: This is a case series of four pediatric patients that were seen between June and September 2021. The patients presented with varied clinical symptoms including confusion, somnolence, seizure-like activity, hypotension, and tachycardia after exposure to delta-8-THC products obtained in retail shops. Basic urine drug screen immunoassays revealed positive results for cannabinoids in all patients. Subsequent confirmatory drug analysis of residual biological samples of blood and/or urine was sent to the University of California San Francisco Clinical Toxicology and Environment Biomonitoring Laboratory with the assistance of the Drug Enforcement Administration's Toxicology Testing Program (DEA TOX). Confirmatory testing revealed 11-nor-9-carboxy-delta-8-THC, the metabolite of delta-8-THC. Delta-9-THC and its metabolites were not detected on confirmatory testing in any of the cases. DISCUSSION: Clinical effects of delta-8-THC in children include but are not limited to altered mental status, seizure-like activity, and vital sign abnormalities. Delta-8-THC exposure may lead to a positive urine drug screen for cannabinoids, but confirmatory testing is needed to differentiate from delta-9-THC.

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.

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.

Ivermectin associated adverse events in the treatment and prevention of COVID-19 reported to the FACT pharmacovigilance project.

BACKGROUND: In August 2021, the Centers for Disease Control and Prevention (CDC) released a health alert following the rapid increase in ivermectin prescriptions and reports of severe illness associated with use of products containing ivermectin for the prevention or treatment of COVID-19 infections. The United States Food and Drug Administration (FDA) and the CDC have explicitly discouraged the use of ivermectin in the prevention or treatment of COVID-19 outside of clinical trials. The study aims to describe the adverse events (AEs) related to ivermectin use for the prevention or treatment of COVID-19. METHODS: This is a prospective case series of adverse events related to therapeutics used in the prevention or treatment of COVID-19 submitted to the FDA ACMT COVID-19 ToxIC (FACT) Pharmacovigilance Project sub-registry between October 2020 and December 2021. This is an ongoing toxico-surveillance system at 15 major academic medical centers in 12 states. Data collected included sociodemographics, exposure related information including dose, frequency, route, duration, and reason for taking ivermectin as well as a clinical description of the adverse event and the outcome. RESULTS: A total of 40 patients who developed AEs following ivermectin use were reported to FACT over 15 months. Self-medication with veterinary formulations were reported in 18/40 patients Thirty-three patients presented to emergency departments and nineteen patients were admitted to the hospital. Patients reported using ivermectin for prevention (24/40), treatment of symptoms (19/40), and for treatment of documented COVID-19 (8/40). Neurological toxicity was the most frequent finding. Fifteen patients had minor symptoms while 25 developed severe toxicity. CONCLUSIONS: Ivermectin use for the attempted treatment of COVID-19 has potential adverse health effects primarily related to neurological function. This is especially true when patients are self-treating with this medication and when they are using formulations intended for non-human use.

Seniors and single-use detergent sacs (SUDS): a review of the National Poison Data System from 2012 to 2020.

INTRODUCTION: Exposure to single-use detergent sacs (SUDS), or laundry pods, have declined in the pediatric population between 2015 and 2018. Older adult exposures are less well described, and it is unclear if there is an increased risk of unintentional exposure to SUDS in older adults, especially in those with dementia. This study aims to review SUDS exposures in adults greater than 60-year-old between 2012 and 2020. METHODS: Using the National Poison Data System (NPDS), a query was performed for cases involving an acute single substance exposure with substance coded as "laundry detergent unit dose" (Generic code: 0201181, 0201182, and 0201183) in adults greater than 60-years-old between January 1, 2012 and December 31, 2020. Exclusion criteria included unknown age, age less than 60 years, any multi-substance exposure, and chronic or acute-on-chronic acuity. The distribution of cases was analyzed for demographics, exposure circumstances, management, clinical effects, and medical outcome. RESULTS: SUDS exposure reported to NPDS increased from 46 cases in 2012 to 219 cases in 2020. Among the 1289 total reported cases, 94.9% (n = 1223) were unintentional exposures with an average age of 75-year-old. The majority of exposures occurred in females (69%, n = 883). More than 1 exposure route was reported in 90 cases (7%), and the most common route of exposure was ingestion (64.9%, n = 836). Major effects were identified in 1% (n = 13) of exposures, and 0.5% (n = 7) of cases resulted in death. CONCLUSIONS: Despite a declining incidence of pediatric SUDS exposure, older adult exposures have increased over 400% between 2012 and 2020.

Identification of a novel opioid, N-piperidinyl etonitazene (etonitazepipne), in patients with suspected opioid overdose.

BACKGROUND: Novel opioids in the illicit drug supply, such as the "nitazene" group of synthetic opioids, present an ongoing public health problem due to high potency and respiratory depressant effects. We describe three patients in whom N-piperidinyl etonitazene, a compound not previously reported in human exposure, was detected after suspected opioid overdose. Other substances that these patients tested for included fentanyl, cocaine, levamisole, phenacetin, benzoylecgonine, para-fluorofentanyl, presumptive heroin (tested as 6-monoacetylmorphine (6-MAM), morphine, and codeine), and tramadol. METHODS: This is a case series of patients with acute opioid overdose enrolled in an ongoing multicenter prospective cohort study. Data collected included reported substance use, clinical course, naloxone dose and response, outcome, and analytes detected in biological samples. RESULTS: Between October 6, 2020 and October 31, 2021, 1006 patients were screened and 412 met inclusion criteria. Of these, three patients (age 33-55) tested positive for N-piperidinyl etonitazene at one site in New Jersey over a period of three days in July 2021. Two patients reported the use of cocaine; one reported the use of heroin and alprazolam. All three patients received naloxone with improvement in their mental status (2 milligrams (mg) intranasally (IN); 8 mg IN; 0.08 mg intravenous (IV)). Two of three received subsequent doses for recurrence of opioid toxicity (0.4-0.6 mg IV). One patient was diagnosed with pneumonia and admitted to the intensive care unit, one was discharged from the Emergency Department (ED), and one used additional drug while in the ED and required admission for a naloxone infusion. None developed organ damage or sequelae. CONCLUSION: These cases represent a local outbreak of a novel "nitazene" opioid. Public health toxicosurveillance should incorporate routine testing of this emerging class of synthetic compounds in the illicit drug supply.