The Toxicology Investigators Consortium 2023 Annual Report.

Since 2010, the American College of Medical Toxicology (ACMT) Toxicology Investigators Consortium (ToxIC) has maintained the ToxIC Core Registry, a national case registry of in-hospital and clinic patient consultations submitted by medical toxicology physicians. Deidentified 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 fourteenth annual report provides data from 7392 patients entered into the Core Registry in 2023 by 36 participating sites comprising 61 distinct healthcare facilities, bringing the total case count to 102331 between 2010 and 2023. Ethanol was the most commonly reported exposure agent class (24.4%), followed by opioids (22.7%), non-opioid analgesics (16.7%), and antidepressants (11.7%). For the first time since the registry's initiation, in 2023, ethanol was the leading agent of exposure. There were 98 fatalities (case fatality rate of 1.3%). Additional descriptive analyses in this annual report were conducted to describe the reasons for medical toxicology consultation by age in 2023, and yearly trends for opioid and psychoactive exposures, physostigmine and rivastigmine treatments, and acetaminophen exposures treated with fomepizole.

Suspected Counterfeit M-30 Oxycodone Pill Exposures and Acute Withdrawals Reported from a Single Hospital - Toxicology Investigators Consortium Core Registry, U.S. Census Bureau Western Region, 2017-2022.

Availability of counterfeit prescription pills (counterfeit pills) containing illegally made fentanyl, including counterfeit M-30 oxycodone (counterfeit M-30) pills, has risen sharply in the United States and has been increasingly linked to overdose deaths. In 2023, approximately 115 million counterfeit pills were seized in U.S. High Intensity Drug Trafficking Areas. However, clinical data on counterfeit pill-related overdoses are limited. Medical toxicology consultations during 2017-2022 from one U.S. Census Bureau Western Region hospital participating in the Toxicology Investigators Consortium Core Registry were analyzed. A total of 352 cases suspected to involve counterfeit M-30 pills, including 143 (40.6%) cases of fentanyl exposure and 209 (59.4%) cases of acute withdrawal were identified; consultations increased from three in 2017, to 209 in 2022. Patients aged 15-34 years accounted for 95 (67.4%) exposure cases. Among all patients with exposures, 81.1% were hospitalized, 69.0% of whom were admitted to an intensive care unit. Additional substances were detected in 131 (91.6%) exposures. Providing outreach to younger persons misusing prescription pills, improving access to and distribution of harm reduction tools including fentanyl test strips and naloxone, and promoting linkage of persons treated for overdose in hospitals to harm reduction and substance use treatment services are strategies to reduce morbidity associated with use of counterfeit M-30.

A Decade in Review: Trends in Female Authorship in Peer-Reviewed Toxicology Journals.

BACKGROUND: Gender diversity in both emergency medicine and medical toxicology has grown over the last decade. However, disparities in promotion, awards, and speakership still exist. No studies have examined gender disparities in authorship in medical toxicology journals. RESEARCH QUESTIONS: Does the proportion of female first authors and female senior authors in medical toxicology publications increase over time? What factors predict female authorship in the first author or last author positions in two major medical toxicology journals? METHODS: We performed a retrospective review of all non-abstract publications in two medical toxicology journals, Clinical Toxicology and Journal of Medical Toxicology, between 2011 and 2020. We collected author names, number of authors, publication type, and publication year. Author names were used to identify author gender using Gender-API integrative tool. Data on the percentages of female medical toxicology fellows and medical toxicologists was provided by the American Board of Emergency Medicine (ABEM). RESULTS: A total of 2212 publications were reviewed and 2171 (97.9%) were included in the dataset. Overall, 31.7% of first authors were identified as female and 67.0% were identified as male by the Gender-API tool. There were 46.8% male-male author dyads, 24.2% female-male author dyads, 12.1% male-female author dyads, and 5.7% female-female author dyads. Predictors of female first authorship included research and case report articles, and percentage of ABEM female toxicologists. Predictors of female senior authorship included number of authors and percentage of ABEM female toxicologists. The proportion of female authorship in both categories increased over the study period. CONCLUSIONS: The frequency of female authorship in the first author position has grown over the last decade and is associated with increasing female representation in medical toxicology and specific manuscript subtypes, specifically research manuscripts.

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.

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.

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.

The Toxicology Investigators Consortium Case Registry-the 2021 Annual Report.

The Toxicology Investigators Consortium (ToxIC) Core Registry was established by the American College of Medical Toxicology in 2010. The Core Registry collects data from participating sites with the agreement that all bedside and telehealth medical toxicology consultations will be entered. This twelfth annual report summarizes the registry's 2021 data and activity with its additional 8552 cases. Cases were identified for inclusion in this report by a query of the ToxIC database for any case entered from January 1 to December 31, 2021. Detailed data was collected from these cases and aggregated to provide information, which included demographics, reason for medical toxicology evaluation, agent and agent class, clinical signs and symptoms, treatments and antidotes administered, mortality, and whether life support was withdrawn. Gender distribution included 50.4% of cases in females, 48.2% of cases in males, and 1.4% of cases in transgender or gender non-conforming individuals. Non-opioid analgesics were the most commonly reported agent class (14.9%), followed by opioids (13.1%). Acetaminophen was the most common agent reported. Fentanyl was the most common opioid reported and was responsible for the greatest number of fatalities. There were 120 fatalities, comprising 1.4% of all cases. Major trends in demographics and exposure characteristics remained similar to past years' reports. Sub-analyses were conducted to describe new demographic characteristics, including marital status, housing status and military service, the continued COVID-19 pandemic and related toxicologic exposures, and novel substances of exposure.

Late hemotoxicity following North American rattlesnake envenomation treated with crotalidae immune F(ab')2 (equine) antivenom and crotalidae immune polyvalent Fab (ovine) antivenom reported to the North American Snakebite Sub-registry.

INTRODUCTION: Late hemotoxicity is common following rattlesnake envenomation treated with crotalidae immune polyvalent Fab (ovine) (FabAV). Initial clinical trials showed crotalidae immune F(ab')2 (equine) (Fab2AV) to be superior to FabAV in preventing late hemotoxicity, but this effect has not been demonstrated in broader populations. This study investigated late hemotoxicity in patients receiving Fab2AV or FabAV after rattlesnake envenomation. METHODS: This is a retrospective analysis of prospectively collected data from patients with snakebite reported to the ToxIC North American Snakebite Registry (NASBR) between January 1, 2019, and December 31, 2020. Inclusion criteria were rattlesnake envenomation and administration of antivenom. Patients were excluded if they received more than one type of antivenom. The primary outcome was occurrence of late hemotoxicity (platelets ≤120 k/mm3 or fibrinogen ≤170 mg/dL) in patients receiving Fab2AV and FabAV. Data collected included demographics, envenomation characteristics, laboratory values, and treatment administered. Statistics including t-test and Fisher's exact test were used. RESULTS: A total of 201 rattlesnake envenomated patients receiving antivenom were reported to the NASBR in the study period; 144 were included. 49 received Fab2AV alone, 45 received FabAV alone and 50 received both antivenoms. Baseline patient and envenomation characteristics were similar between the groups. Late hemotoxicity occurred in 2/49 patients in the Fab2AV group (4% (95% CI 0.7-12.6)) and in 19/45 patients in the FabAV group (42% (95% CI 28.4-59.0); absolute risk reduction 39.1% (95% CI 21.2-46.2) (p = 0.001). On follow up, 0 patients (0%) receiving Fab2AV were retreated with antivenom; 4 patients (9%) receiving FabAV were retreated (p = 0.049). CONCLUSIONS: In the North American Snakebite Registry, late hemotoxicity was less common in rattlesnake envenomated patients treated with Fab2AV compared to FabAV.

Early Experience with Crotalidae Immune F(ab')2 Antivenom to Treat Arizona Rattlesnake Envenomations.

INTRODUCTION: Crotalidae immune F(ab')2 (Fab2AV) became available in the USA in 2019 for treatment of rattlesnake envenomation. In the clinical trial comparing Fab2AV to crotalidae immune polyvalent fab (FabAV), Fab2AV was associated with less late hemotoxicity. The purpose of this study was to describe outcomes following use of Fab2AV in patients with rattlesnake envenomation in Arizona. METHODS: This is an observational study of patients admitted to a medical toxicology service at two hospitals in Arizona between January 1, 2019 and December 31, 2020. Patients with rattlesnake envenomation who received Fab2AV were included. Patients who received FabAV, alone or in combination with Fab2AV, were excluded. The main outcomes of interest were antivenom dose, adverse reactions, late hemotoxicity, and hospital readmission or retreatment. RESULTS: Forty-six patients were included. The mean age was 40 years, with 15% under 12 years of age. All exhibited swelling, 20% thrombocytopenia, and 35% coagulopathy. Median time to treatment was 3 h and median total Fab2AV dose was 20 vials. Three patients had an acute reaction to Fab2AV which was non-life-threatening and resolved with antihistamines and/or steroids. In the follow-up period, one case of delayed thrombocytopenia (platelets = 108 K/mm3) and one case of recurrent thrombocytopenia (platelets = 111 K/mm3) were identified. There was no late coagulopathy. Five patients reported symptoms consistent with mild serum sickness. CONCLUSIONS: In this series of patients with rattlesnake envenomation in Arizona who were treated with Fab2AV, there were no cases of clinically significant late hemotoxicity, and no patients required late retreatment with antivenom. Acute and delayed reactions did occur in some patients but were mild and easily treated.

The Toxicology Investigators Consortium 2020 Annual Report.

The Toxicology Investigators Consortium (ToxIC) Registry was established by the American College of Medical Toxicology in 2010. The registry collects data from participating sites with the agreement that all bedside and telehealth medical toxicology consultation will be entered. This eleventh annual report summarizes the Registry's 2020 data and activity with its additional 6668 cases. Cases were identified for inclusion in this report by a query of the ToxIC database for any case entered from January 1 to December 31, 2020. Detailed data was collected from these cases and aggregated to provide information which included demographics, reason for medical toxicology evaluation, agent and agent class, clinical signs and symptoms, treatments and antidotes administered, mortality, and whether life support was withdrawn. Gender distribution included 50.6% cases in females, 48.4% in males, and 1.0% identifying as transgender. Non-opioid analgesics were the most commonly reported agent class, followed by opioid and antidepressant classes. Acetaminophen was once again the most common agent reported. There were 80 fatalities, comprising 1.2% of all registry cases. Major trends in demographics and exposure characteristics remained similar to past years' reports. Sub-analyses were conducted to describe race and ethnicity demographics and exposures in the registry, telemedicine encounters, and cases related to the COVID-19 pandemic.

Delayed peaks of acetaminophen in overdose patients with concomitant abdominal trauma.

OBJECTIVE: To present two cases of delayed acetaminophen absorption in abdominal trauma patients with concomitant acetaminophen overdose. CASES: Case 1. A 25-year-old female arrived to the emergency department with multiple stab wounds. She had ingested an unknown amount of acetaminophen and was then stabbed by her boyfriend in a suicide pact. Initial acetaminophen concentration was 211.7 mcg/mL and the patient was started on N-Acetylcysteine (NAC) therapy. She was found to have injuries and was taken for operative repair. Acetaminophen concentrations were down trending and nearly undetectable until 58 h post-presentation when concentrations began to rise again. CASE 2: A 41-year-old female ingested approximately 500 tablets of acetaminophen prior to jumping from a four-story building in a suicide attempt. She was found to have multiple traumatic injuries as well as an initial acetaminophen concentration of 225 mcg/mL and was started on NAC therapy. The patient underwent multiple interventions to treat her traumatic injuries. Despite receiving no acetaminophen while inpatient, the patient's acetaminophen concentrations peaked a second time on her third hospital day. CONCLUSIONS: In this case series, two patients with abdominal trauma and coexistent massive acetaminophen ingestions were described. Both cases demonstrated a delayed rise in serum acetaminophen concentrations and required extended NAC therapy.

The Toxicology Investigators Consortium Case Registry-the 2019 Annual Report.

The Toxicology Investigators Consortium (ToxIC) Registry was established by the American College of Medical Toxicology (ACMT) in 2010. The Registry collects data from participating sites with the agreement that all bedside medical toxicology consultation will be entered. This tenth annual report summarizes the Registry's 2019 data and activity with its additional 7177 cases. Cases were identified for inclusion in this report by a query of the ToxIC database for any case entered from 1 January to 31 December 2019. Detailed data was collected from these cases and aggregated to provide information which included demographics, reason for medical toxicology evaluation, agent and agent class, clinical signs and symptoms, treatments and antidotes administered, mortality, and whether life support was withdrawn. 50.7% of cases were female, 48.5% were male, and 0.8% were transgender. Non-opioid analgesics was the most commonly reported agent class, followed by opioid and antidepressant classes. Acetaminophen was once again the most common agent reported. There were 91 fatalities, comprising 1.3% of all Registry cases. Major trends in demographics and exposure characteristics remained similar to past years' reports. Sub-analyses were conducted to describe exposures in cases of self-harm, gender differences in substance use disorder, and trends in addiction medicine and pain management consultations.

Identification and management of marine envenomations in pediatric patients

Marine envenomations can cause a diverse array of clinical syndromes. Systemic and life-threatening reactions, as well as delayed presentations, can occur. The pediatric population is at higher risk for serious reactions to envenomations because their greater body surface area and smaller body mass can lead to a higher relative venom load. Although the majority of the literature on marine envenomations is of low quality, the available literature does suggest that management varies depending on the geographic location. This issue reviews both common and life-threatening presentations of marine envenomations, highlights key aspects of the history and physical examination that will help narrow the differential, and offers recommendations for management based on the envenomating creature and geographic location.

Exploratory Ingestions of Novel Anticoagulants and Antiplatelets: What Is the Risk?

BACKGROUND: Historically, anticoagulants and antiplatelet agents included warfarin and aspirin, respectively. In recent years, numerous novel anticoagulants (eg, direct thrombin inhibitors and factor Xa inhibitors) as well as the adenosine diphosphate receptor antagonists have increased significantly. Little information on the bleeding risk after exploratory ingestion of these agents is available. The primary purpose of this study is to evaluate the bleeding risk of these agents after an exploratory ingestion in children 6 years or younger. METHODS: This retrospective multicenter poison control center study was conducted on calls between 2005 and 2014. The following agents were included: apixaban, clopidogrel, dabigatran, edoxaban, prasugrel, rivaroxaban, or ticagrelor. Bleeding characteristics and treatment rendered were recorded. RESULTS: A total of 638 cases were identified. Most cases involved antiplatelet agents. No patient developed any bleeding complication. The administration of charcoal was independent of the amount of drug ingested. CONCLUSION: Accidental, exploratory ingestions of these agents seem well tolerated, with no patient developing bleeding complications.

The Toxicology Investigators Consortium Case Registry-the 2018 Annual Report.

The Toxicology Investigators Consortium (ToxIC) Registry was established by the American College of Medical Toxicology (ACMT) in 2010. The Registry collects data from participating sites with the agreement that all bedside medical toxicology consultation will be entered. The objective of this ninth annual report is to summarize the Registry's 2018 data and activity with its additional 7043 cases. Cases were identified for inclusion in this report by a query of the ToxIC database for any case entered from 1 January to 31 December 2018. Detailed data was collected from these cases and aggregated to provide information which included demographics, reason for medical toxicology evaluation, agent and agent class, clinical signs and symptoms, treatments and antidotes administered, mortality, and whether life support was withdrawn. A total of 51.5% of cases were female, 48% were male, and 0.6% transgender. Non-opioid analgesics were the most commonly reported agent class, followed by antidepressants and opioids. Acetaminophen was once again the most common agent reported. There were 106 fatalities, comprising 1.5% of all registry cases. Major trends in demographics and exposure characteristics remained similar to past years' reports. Sub-analyses were conducted to describe exposures in elderly patients, addiction consultation practices, and risk factors for bupropion-induced seizures. The launch of the ToxIC Qualified Clinical Data Registry (TQCDR) is also described.