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With the gender composition of the membership in mind, ACMT appears to be doing well, although review of ACMT awards reveals there is still room for improvement. Through conscious attention and focus on gender issues, Medical Toxicology as a specialty has the opportunity to lead in creating a more gender-balanced framework for career advancement in academic medicine and a more equitable environment for all. Gender differences in attending physicians' feedback to residents: a qualitative analysis. [Extracted from the article]

A letter to the editor is presented in response to the article "2010 American Heart Association and American Red Cross Guidelines for First Aid," by D. Markenson and colleagues in the October 2010 issue.

The international boundaries to medical education are becoming less marked as new technologies such as multiuser videoconferencing are developed and become more accessible to help bridge the communication gaps. The Global Educational Toxicology Uniting Project (GETUP) is aimed at connecting clinicians in countries with established clinical toxicology services to clinicians in countries without clinical toxicologists around the globe. Centers that manage or consult on toxicology cases were registered through the American College of Medical Toxicology website via Survey Monkey ®. Data was analyzed retrospectively from February 2014 to January 2015. Google hangouts ® was used as the main conferencing software, but some sites preferred the use of Skype ®. Registration data included contact details and toxicology background and qualifications. Thirty sites in 19 different countries in Australasia, Europe, Africa, and America were registered. Twenty-eight (93 %) sites were located in a major urban center, one (3.5 %) site in a major rural center and one (3.5 %) a private practice. Expectations of GETUP included sharing toxicology cases and education (30, 100 % of sites), assistance with toxicology management guidelines (2, 7 %), assistance with providing a toxicology teaching curriculum in languages other than English (2, 7 %), and managing toxicology presentations in resource-poor settings, international collaboration, and toxicovigilance (2 sites, 7 %). Twenty-two conferences were performed during the first 12 months with a mean of 3 cases per conference. GETUP has connected countries and clinical units with and without toxicology services and will provide a platform to improve international collaboration in clinical toxicology. [ABSTRACT FROM AUTHOR]

The primary objective is to identify and describe the complications associated with the use of intravenous lipid emulsion (ILE) therapy as an antidote for lipophilic drug toxicity. This study is a retrospective chart review of patients treated with ILE at two academic medical centers between 2005 and 2012. Based on previously reported complications, we hypothesized that pancreatitis, ARDS, and lipemia-induced laboratory interference might occur. Clinical definitions of these complications were defined a priori. Subjects treated with ILE who did not develop at least one complication were excluded. A total of nine patients were treated with ILE during the study period, six of whom experienced potential complications as a result of the ILE. Two patients developed pancreatitis, and four patients had lipemia-induced interference of interpretation of laboratory studies, despite ultracentrifugation. Laboratory interference precluded one patient from being an organ donor. Three patients developed ARDS; although temporally associated, a causal relationship between ILE and the development of ARDS cannot be clearly established. As ILE is increasingly used for less severe cases of drug toxicity, clinicians should be aware of potential complications associated with its use. A risk-benefit assessment for the use of ILE should be implemented on a case-by-case basis. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The technology of antivenom production has gradually changed since the earliest production of antisera around the turn of the 20th century. Use of early antisera was associated with frequent acute adverse reactions and serum sickness. New F(ab')2 products, manufactured using pepsin degradation of immunoglobulin together with precipitation of unwanted protein and albumin serum fractions, should in concept cause fewer immune reactions in clinical use. Methods: A linked set of five prospective clinical trials of an equine F(ab')2 antivenom, together with one historical control study, were completed during development of the product for a Biological License Application through the US FDA. Adverse events were recorded and categorized, with particular attention to the frequency of immune reactions. Results: A total of 1534 patients ages 0.1–90.5 years received antivenom, in Arizona and in Mexico, for treatment of scorpion envenomation. Total dosing ranged from 1 to 5 vials except for one outlier who received 10 vials. Estimated protein exposure was 12–275 mg per patient (outlier, up to 550 mg). Three patients (0.2%) had acute reactions to antivenom infusion (one urticaria, one urticaria and dyspnea, and one panic attack). Eight (0.5%) had rashes suggestive of Type 3 immune reactions, although none had the full syndrome of serum sickness. Two women were treated for envenomation during the first trimester of pregnancy, one of whom subsequently experienced a spontaneous abortion. Conclusions: Rates of immune reaction to this product were two orders of magnitude lower than the range (up to 75% for early and 81% for late reactions) historically reported with use of minimally refined whole immunoglobulin products against a variety of infections and envenomations. Lower protein dose, greater purity of the active component, lack of the immunogenic Fc portion of the immunoglobulin molecule, and slow intravenous infusion are likely to be the reason for this. Clinical implications of a safer product include that it can be employed in settings where antivenom was once considered too dangerous to use, such as primary care clinics and remote rural areas. [Copyright &y& Elsevier]

Introduction : Scorpion envenomation is potentially life-threatening and affects children in the Southwestern USA. An FDA-approved antivenom is available, but its high cost has led to use of off-label antivenom dosing or supportive care alone as alternatives to FDA-recommended dosing. This study sought to determine whether treatment approach influences outcomes in envenomated children. Methods: A retrospective cohort study of children with grade III or IV scorpion envenomation evaluated in Phoenix Children's Hospital ED between September 1, 2011, and March 31, 2014. Patients were grouped based on treatment: group 1, supportive care only; group 2, FDA-recommended dosing (3-vial initial dose); group 3, 'off label' dosing (1-2 vial initial dose). Primary outcomes were ED length of stay and hospital admission. Secondary outcomes were mechanical ventilation and aspiration pneumonia. Results: One hundred fifty-six patients were included with 58 patients in group 1, 16 patients in group 2, and 82 patients in group 3. Group 1 was significantly older than the antivenom groups ( p < 0.001), and group 2 was younger than group 3 ( p = 0.024). Envenomation grade was also different, with group 1 having fewer grade IV then groups 2 and 3 ( p < 0.001). Three percent of group 1, 56 % of group 2, and 28 % of group 3 had respiratory distress ( p < 0.001). ED LOS was not significantly different between groups. Hospital admission occurred in 3.4 % group 1, no group 2, and 8.5 % group 3 patients. Two intubations and two aspirations occurred in group 3. Conclusions: In this study, clinical presentation appeared to influence treatment. Groups that received antivenom had a higher envenomation grade than the group that received supportive care. The FDA-recommended dosing group was younger and had more respiratory distress than those treated with initial doses of 1-2 vials. Outcomes were not significantly different between groups. Prospective studies may identify the ideal population for each treatment approach. [ABSTRACT FROM AUTHOR]

The American College of Medical Toxicology established the Toxicology Investigators Consortium (ToxIC) Case Registry in 2010. The Registry contains all medical toxicology consultations performed at participating sites. The Registry has continued to grow since its inception, and as of December 31, 2015, contains 43,099 cases. This is the sixth annual report of the ToxIC Registry, summarizing the additional 8115 cases entered in 2015. Cases were identified by a query of the Registry for all cases entered between January 1 and December 31, 2015. Specific data reviewed for analysis included demographics (age, race, gender), source of consultation, reason for consultation, agents and agent classes involved in exposures, signs, symptoms, clinical findings, fatalities, and treatment. By the end of 2015, there were 50 active sites, consisting of 101 separate health-care facilities; 51.2 % of cases involved females. Adults between the ages of 19 and 65 made up the majority (64.2 %) of Registry cases. Caucasian race was the most commonly reported (55.6 %); 9.6 % of cases were identified as Hispanic ethnicity. Inpatient and emergency department referrals were by far the most common referral sources (92.9 %). Intentional pharmaceutical exposures remained the most frequent reason for consultation, making up 52.3 % of cases. Of these intentional pharmaceutical exposures, 69 % represented an attempt at self-harm, and 85.6 % of these were a suicide attempt. Nonopioid analgesics, sedative-hypnotics, and antidepressant agents were the most commonly reported agent classes in 2015. Almost one-third of Registry cases involved a diagnosed toxidrome (32.8 %), with a sedative-hypnotic toxidrome being the most frequently described. Significant vital sign abnormalities were recorded in 25.3 % of cases. There were 98 fatalities reported in the Registry (1.2 %). Adverse drug reactions were reported in 4.3 % of cases. Toxicological treatment was given in 65.3 % of cases, with 33.0 % receiving specific antidotal therapy. Exposure characteristics and trends overall were similar to prior years. While treatment interventions were required in the majority of cases, fatalities were rare. [ABSTRACT FROM AUTHOR]

Elevated concentrations of serum acetaminophen-protein adducts, measured as protein-derived acetaminophen-cysteine (APAP-CYS), have been used to support a diagnosis of APAP-induced liver injury when histories and APAP levels are unhelpful. Adducts have been reported to undergo first-order elimination, with a terminal half-life of about 1.6 days. We wondered whether renal failure would affect APAP-CYS elimination half-life and whether continuous venovenous hemodiafiltration (CVVHDF), commonly used in liver failure patients, would remove adducts to lower their serum concentrations. Terminal elimination half-lives of serum APAP-CYS were compared between subjects with and without renal failure in a prospective cohort study of 168 adults who had ingested excessive doses of APAP. APAP-CYS concentrations were measured in plasma ultrafiltrate during CVVHDF at times of elevated serum adduct concentrations. Paired samples of urine and serum APAP-CYS concentrations were examined to help understand the potential importance of urinary elimination of serum adducts. APAP-CYS elimination half-life was longer in 15 renal failure subjects than in 28 subjects with normal renal function (41.3 ± 2.2 h versus 26.8 ± 1.1 h [mean ± SEM], respectively, p < 0.001). CVVHDF failed to remove detectable amounts of APAP-CYS in any of the nine subjects studied. Sixty-eight percent of 557 urine samples from 168 subjects contained no detectable APAP-CYS, despite levels in serum up to 16.99 μM. Terminal elimination half-life of serum APAP-CYS was prolonged in patients with renal failure for reasons unrelated to renal urinary adduct elimination, and consideration of prolonged elimination needs to be considered if attempting back-extrapolation of adduct concentrations. CVVHDF did not remove detectable APAP-CYS, suggesting approximate APAP-protein adduct molecular weights ≥ 50,000 Da. The presence of urinary APAP-CYS in the minority of instances was most compatible with renal adduct production and protein shedding into urine rather than elimination of serum adducts. [ABSTRACT FROM AUTHOR]

Warfarin, a vitamin K antagonist, is widely used for the prophylaxis and treatment of thromboembolic disease. While guidelines exist for management of a supratherapeutic international normalized ratio following therapeutic warfarin use, these guidelines are not designed for management of the acute warfarin overdose. There is a paucity of literature describing the latter. The primary objective of this manuscript is to characterize the coagulopathy and describe the bleeding events that occur after a warfarin overdose. A secondary goal is to describe the amount of vitamin K administered to patients presenting with warfarin overdoses. A retrospective chart review of patients admitted with an acute warfarin overdose at two tertiary care medical centers in the USA was conducted. Clinical characteristics were abstracted, and bleeding categories (major, minor, trivial) were defined a priori. Twenty-three patients were admitted during the time period; males accounted for 15/23 (62.5 %) subjects. The median (interquartile range (IQR)) age was 43 (32-48.5) years. Seventeen subjects received vitamin K, with a median (IQR) dose of 15 (10-50) mg. The maximal total amount of vitamin K administered to a single patient during the index hospitalization was 110 mg. Three bleeding events occurred; one classified as major, and two as minor. All patients made a full recovery. In this case series of acute warfarin overdose, nearly all patients developed a coagulopathy, and nearly three-quarters of patients received vitamin K. Bleeding events occurred in a minority of patients. [ABSTRACT FROM AUTHOR]

This is the third article of a three-part series that reviews the care of poisoned patients in the ICU. This article focuses on natural toxins, such as heavy metals and those produced by plants, mushrooms, arthropods, and snakes. The first article discussed the general approach to the patient, including laboratory testing; the second article focused on specific toxic agents, grouped into categories. [ABSTRACT FROM AUTHOR]

Poisonings, adverse drug effects, and envenomations continue to be commonly encountered. Patients often present critically ill and warrant ICU admission. Many other patients who are initially stable have the potential for rapid deterioration and require continuous cardiopulmonary and neurologic monitoring. Given the potential for rapid deterioration, and because patients need continuous monitoring, ICU admission is frequently required. This article is the first of a three-part series to be published in CHEST; it discusses general management, laboratory tests, enhanced elimination, and emerging therapies. The second article will address the management of specific overdoses; the last will cover plants, mushrooms, envenomations, and heavy metals. [ABSTRACT FROM AUTHOR]

Abstract Background Envenomation by crotaline snakes (rattlesnake, cottonmouth, copperhead) is a complex, potentially lethal condition affecting thousands of people in the United States each year. Treatment of crotaline envenomation is not standardized, and significant variation in practice exists. Methods A geographically diverse panel of experts was convened for the purpose of deriving an evidence-informed unified treatment algorithm. Research staff analyzed the extant medical literature and performed targeted analyses of existing databases to inform specific clinical decisions. A trained external facilitator used modified Delphi and structured consensus methodology to achieve consensus on the final treatment algorithm. Results A unified treatment algorithm was produced and endorsed by all nine expert panel members. This algorithm provides guidance about clinical and laboratory observations, indications for and dosing of antivenom, adjunctive therapies, post-stabilization care, and management of complications from envenomation and therapy. Conclusions Clinical manifestations and ideal treatment of crotaline snakebite differ greatly, and can result in severe complications. Using a modified Delphi method, we provide evidence-informed treatment guidelines in an attempt to reduce variation in care and possibly improve clinical outcomes.

Objectives: This study compares maintenance with clinical- and laboratory-triggered (as-needed [PRN]) antivenom dosing strategies with regard to patient-centered outcomes after rattlesnake envenomation.Design: This is a retrospective cohort study of adult rattlesnake envenomations treated at a regional toxicology center. Data on demographics, envenomation details, antivenom administration, length of stay, and laboratory and clinical outcomes were compared between the PRN and maintenance groups. Primary outcomes were hospital length of stay and total antivenom used, with a hypothesis of no difference between the two dosing strategies.Setting: A single regional toxicology center PATIENTS:: Three-hundred ten adult patients envenomated by rattlesnakes between 2007 and 2014 were included. Patients were excluded if no antivenom was administered or for receiving an antivenom other than Crofab (BTG International, West Conshohocken, PA).Interventions: This is a retrospective study of rattlesnake envenomations treated with and without maintenance antivenom dosing.Main Results: One-hundred forty-eight in the maintenance group and 162 in the PRN group were included. There was no difference in demographics or baseline envenomation severity or hemotoxicity (32.7% vs 40.5%; respectively; p = 0.158) between the two groups. Comparing the PRN with the maintenance group, less antivenom was used (8 [interquartile range, 6-12] vs 16 [interquartile range, 12-18] vials, respectively; p < 0.001), and hospital length of stay was shorter (27 hr [interquartile range, 20-44 hr] vs 34 hr [interquartile range, 24-43 hr], respectively; p = 0.014). There were no differences in follow-up outcomes of readmission, retreatment, or bleeding and surgical complications.Conclusions: Hospital length of stay was shorter, and less antivenom was used in patients receiving a PRN antivenom dosing strategy after rattlesnake envenomation. [ABSTRACT FROM AUTHOR]

The geographic variation of Mohave rattlesnake ( Crotalus scutulatus ) venom is well established. We reviewed all the Mohave rattlesnake bites reported to the Toxicology Investigators Consortium's North American Snakebite Registry between January 1, 2015 and 12/31/2021. Data reviewed for this study included details regarding the snake encounter, patient demographics, signs and symptoms, treatment, and outcomes. Our objective was to describe the epidemiology, clinical manifestations, and management of Mohave rattlesnake envenomations using prospective data from two geographically distinct sites. There were 20 subjects, including eight nonpregnant females. Ages ranged from seven to 75 years, median age 48. Nine of the bites were managed in Arizona and 11 in California. In Arizona, all envenomated patients had local swelling. None had neurological toxicity. In California, swelling was present in nine patients. Neurological effects were observed in five subjects. Four Arizona patients and one California patient had hypotension requiring treatment. Each site had one patient with thrombocytopenia. An Arizona patient who sustained a bite to the face was intubated. Rhabdomyolysis occurred in two California patients. All envenomated patients received antivenom. Mohave rattlesnakes have the potential to cause significant local and/or systemic toxicity. Neurotoxicity was not observed in envenomations from Mohave rattlesnakes that presumably lack Mohave toxin, but hypotension and gastrointestinal signs were more common than in bites from snakes believed to possess Mohave toxin. Neurological toxicity was limited to paresthesias and fasciculations. Significant skeletal or respiratory muscle weakness was not observed in our study population., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

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., (Copyright © 2023 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.)

Importance: The US and Canada currently have no formal published nationwide guidelines for specialists in poison information or emergency departments for the management of acetaminophen poisoning, resulting in significant variability in management., Objective: To develop consensus guidelines for the management of acetaminophen poisoning in the US and Canada., Evidence Review: Four clinical toxicology societies (America's Poison Centers, American Academy of Clinical Toxicology, American College of Medical Toxicology, and Canadian Association of Poison Control Centers) selected participants (n = 21). Led by a nonvoting chairperson using a modified Delphi method, the panel created a decision framework and determined the appropriate clinical management of a patient with acetaminophen poisoning. Unique to this effort was the collection of guidelines from most poison centers in addition to systematic collection and review of the medical literature. Comments from review by external organizations were incorporated before the guideline was finalized. The project began in March 2021 and ended in March 2023., Findings: The search retrieved 84 guidelines and 278 publications. The panel developed guidelines for emergency department management of single or repeated ingestion of acetaminophen. In addition, the panel addressed extended-release formulation, high-risk ingestion, coingestion of anticholinergics or opioids, age younger than 6 years, pregnancy, weight greater than 100 kg, and intravenous acetaminophen use. Differences from current US practice include defining acute ingestion as an ingestion presentation from 4 to 24 hours after overdose was initiated. A revised form of the Rumack-Matthew nomogram was developed. The term massive ingestion was replaced with the term high-risk ingestion and denoted by a specific nomogram line. Other recommendations include specific criteria for emergency department triage, laboratory evaluation and monitoring parameters, defining the role of gastrointestinal decontamination, detailed management of acetylcysteine treatment, associated adverse effects, and stopping criteria for acetylcysteine treatment, as well as criteria for consultation with a clinical toxicologist. Finally, specific treatment considerations, including acetylcysteine dosing, fomepizole administration, and considerations for extracorporeal elimination and transplant evaluation, were addressed., Conclusions and Relevance: This qualitative study provides a consensus statement on consistent evidence-based recommendations for medical, pharmacy, and nursing education and practice to optimize care of patients with acetaminophen poisoning.

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.

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., (© 2022. American College of Medical Toxicology.)

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/mm 3 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.

This review discusses the distinct envenomation syndromes produced by North American species of snakes and arthropods, specifically the Crotalinae subfamily of snakes, which includes cottonmouths, copperheads, and rattlesnakes; coral snakes; Latrodectus and Loxosceles species of arachnid; and Centruroides sculpturatus, the only species of North American scorpion capable of producing an envenomation syndrome. The authors discuss the epidemiology, pathophysiology, and presentation of these syndromes and emphasize the varying degrees to which these syndromes can manifest clinically. Finally, the management of each envenomation syndrome is addressed. Special attention is paid to available antivenoms, their indications for use, and their side effects., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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/mm 3 ) and one case of recurrent thrombocytopenia (platelets = 111 K/mm 3 ) 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., (© 2021. American College of Medical Toxicology.)

Introduction: Amid the global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), chloroquine and hydroxychloroquine were being studied as agents to prevent and treat coronavirus disease 2019. Information about these agents and their effects circulated throughout the general public media, raising the concern for self-directed consumption of both pharmaceutical and non-pharmaceutical products., Case Report: We present two cases of chloroquine toxicity that occurred after ingestion of an aquarium disinfectant that contained chloroquine phosphate in a misguided attempt to prevent infection by SARS-CoV-2. One patient had repeated emesis and survived, while the other was unable to vomit, despite attempts, and suffered fatal cardiac dysrhythmias., Conclusion: These cases illustrate the spectrum of toxicity, varied presentations, and importance of early recognition and management of chloroquine poisoning. In addition, we can see the importance of sound medical guidance in an era of social confusion compounded by the extremes of public and social media.

Introduction: Few of the 5000-8000 snakebites reported to poison control centers annually in the USA are attributed to coral snakes. This study describes Texas coral snake envenomations reported to the North American Snakebite Registry., Methods: All Texas coral snake envenomation cases reported to the registry were identified for the period from January 1, 2015, through December 31, 2019. Data reviewed for this study included details regarding the snake encounter, patient demographics, signs and symptoms, treatment, and outcomes. Descriptive statistics were used to report results., Results: Ten men and four nonpregnant women reported coral snake bites. The median patient age was 15.5 (range 5-72 years). There were 12 upper extremity bites and two bites to the lower extremity. The most common symptoms reported were paresthesias and pain. All subjects had paresthesias, often described as an "electric" sensation. Seven patients described them as painful. The most common clinical findings were erythema and swelling. No patient developed tissue damage, hematotoxicity, rhabdomyolysis, hypotension, weakness, or respiratory symptoms. Thirteen subjects were treated with opioids. Six patients were treated with antiemetics: three prophylactically and two for opioid-induced nausea. One patient developed nausea and non-bloody, nonbilious emesis within 1 hour of the bite, prior to receiving opioids. No patients were treated with antivenom. Antibiotics were not administered to any patient, and no infections were reported., Conclusions: Envenomations from M. tener in Southeast Texas are characterized by painful paresthesias. Mild swelling and erythema are common. Neurotoxicity necessitating antivenom or mechanical ventilation did not occur.

Background: Rattlesnake envenomations are a significant cause of morbidity in the USA. While pediatric rattlesnake envenomations are relatively common, data comparing adult and pediatric patients with rattlesnake envenomations remain limited., Methods: This multi-center retrospective study used the North American Snakebite Registry (NASBR), a sub-registry of the Toxicology Investigator's Consortium (ToxIC). All cases of rattlesnake envenomations between January 1, 2013, and December 31, 2017, which were entered into the NASBR, were reviewed. Clinical and laboratory parameters, as well as treatment and outcome measurements, were compared between adult and pediatric patients., Results: A total of 420 unique cases were identified, including 94 pediatric patients. Adult patients were more likely to be male (76% vs. 62%; OR 1.98) and sustain upper extremity envenomations (57% vs. 25%; OR 4.4). After adjusting for bite location, adults were more likely to exhibit edema compared with pediatric patients. After controlling for envenomation location, there was no difference in rates of necrosis between adult and pediatric patients. Adults exhibited early hematologic toxicity less frequently than pediatric patients, but there was no difference in the rates of late hematologic toxicity. There were no differences in the rates of hypotension or intubation., Conclusion: While adult and pediatric patients have some differences in envenomation characteristics and laboratory parameters, adults and pediatric patients had similar rates of systemic toxicity, severity, length of stay, and late hematologic toxicity.

Introduction: Measurement of serum acetaminophen-protein adducts (APAP-CYS) has been suggested to support or refute a diagnosis of acetaminophen (APAP)-induced hepatotoxicity when ingestion histories are unreliable or unavailable and when circulating APAP concentrations are low or undetectable. Non-APAP overdose patients commonly have used APAP products in non-toxic quantities and, thus, will have measurable APAP-CYS concentrations, even when hepatic injury results from other causes, such as ischemic hepatitis. The relationship between alanine aminotransferase (ALT) activity and APAP-CYS concentration might assist in distinguishing between toxic and non-toxic APAP doses in patients suspected of drug overdose., Methods: We measured serial levels of serum APAP-CYS and ALT activities in 500 overdose patients in whom APAP toxicity was suspected on inpatient admission, but who were then classified at time of discharge and before results of APAP-CYS concentrations were available into three groups: 1) definite APAP group; 2) definitely not APAP group; and 3) indeterminate group. Subjects in the definite and definitely not APAP groups were selected in whom a plasma ALT activity was measured within ± 4 h of a serum APAP-CYS concentration. Regressions with correlation coefficients between APAP-CYS and ALT were calculated for repeat measures in the 335 subjects (908 blood samples) in the definite APAP group and 79 subjects (231 samples) in the definitely not APAP group, with an emphasis on APAP-CYS concentrations and calculation of 95% prediction intervals when ALT was ≥ 1000 IU/L., Results: A strong correlation was found between APAP-CYS and ALT in the definite APAP group over all ALT activities (r = 0.93, p < 0.001; N = 335), and when ALT was > 1000 IU/L (r = 0.82, p < 0.001, N = 144). In the 79 definitely not APAP subjects, no significant correlation was found when ALT exceeded 1000 IU/L (r = 0.04; p = 0.84, N = 32). All subjects in the definitely not APAP group displayed APAP-CYS concentrations < 3 μM. In definitely not APAP subjects, the great majority of APAP-CYS levels were below the 95% prediction interval for APAP-CYS concentrations in definite APAP group subjects when ALT was ≥ 1000 IU/L. However, some definitely not APAP group subjects who had ingested non-toxic doses of APAP displayed APAP-CYS concentrations as high as 2.8 μM in the face of ALT elevation from ischemic hepatitis., Conclusion: The interpretation of serum APAP-CYS concentrations must always be made in light of detailed clinical information and the population being tested, especially because of some overlap in APAP-CYS levels in subjects with and without APAP toxicity.

Background: Crotalidae Polyvalent Immune Fab (Fab Antivenom) is the primary Viperid antivenom used in the United States since 2000. Adverse event data associated with its use are limited. The purpose of this study is to describe the prevalence of acute adverse events associated with the use of Fab antivenom. Methods: The American College of Medical Toxicology's Toxicology Investigators Consortium maintains a prospective case registry of poisoned and envenomated patients managed by medical toxicologists at the bedside. This registry includes the North American Snakebite sub-registry. We performed a review of 438 cases entered into the Snakebite sub-registry. Results: A total of 373 (85.2%) received at least one vial of Fab Antivenom. Forty percent were children. Adverse events occurred in 10 patients (2.7%) of whom six were adults. Rash was the most common adverse event. More severe adverse events (hypotension, bronchospasm, and/or angioedema) occurred in four (1.1%) patients. Prophylaxis was administered prior to Fab antivenom in 4.0%. Eight patients received various treatments for their adverse events. Neither the initial number of Fab antivenom vials, atopic history, nor prior envenomation correlated with the prevalence of adverse events. Discussion: This prevalence of adverse events was lower than in previous studies and in a meta-analysis of 11 studies. The types of adverse events and treatments used are consistent with those in previous reports. There were no prior reports of prophylaxis use with which to compare. Conclusion: The prevalence of Fab antivenom adverse events in the North American Snakebite Registry was 2.7%.

Background: Twitter-based chat groups (tweetchats) structured as virtual journal clubs have been demonstrated to provide value to learners. In order to promote topics in medical toxicology, we developed the #firesidetox tweetchat as a virtual journal club to discuss and disseminate topics in medical toxicology., Methods: A group of medical toxicologists from the American College of Medical Toxicology (ACMT) Public Affairs Committee and editorial board of the Journal of Medical Toxicology (JMT) developed a quarterly one hour tweetchat featuring JMT manuscripts. We gathered basic twittergraphics and used a healthcare hashtag aggregator to measure the number of impressions, participants, and tweets per tweetchat session. A qualitative analysis of important themes from #firesidetox was also completed., Results: During five tweetchats over 12 months, we attracted a mean of 23 participants generating a mean of 150 tweets per #firesidetox tweetchat. Tweets generated a mean of 329,200 impressions (unique user views): these impressions grew by 300% from the first through fifth #firesidetox. The majority of participants self-identified as medical toxicologists or physician learners. Although most were from the USA, participants also came from Australia, Poland, and Qatar. Most tweets centered on medical education and 7.9% tweets were learner-driven or questions asking for a medical toxicologist expert opinion., Conclusion: The #firesidetox attracted a diverse group of toxicologists, learners, and members of the public in a virtual journal club setting. The increasing number of impressions, participants, and tweets during #firesidetox demonstrates the tweetchat model to discuss pertinent toxicology topics is feasible and well received among its participants.

The American College of Medical Toxicology established the North American Snakebite Registry (NASBR), a national database of detailed, prospectively collected information regarding snake envenomation in the United States, in 2013. This report describes the epidemiology, clinical course, and management of snakebites in the NASBR. All cases entered into the NASBR between January 1, 2013 and December 31, 2015 were identified. Descriptive statistics are used to report results. Fourteen sites in 10 states entered 450 snakebites. Native species comprised 99% of cases, almost all of which were pit viper bites. 56.3% were identified as rattlesnakes and 29.4% as copperheads. 69.3% were male and 28.2% were children age 12 and under. Fifty-four percent of bites were on the lower extremity. Twenty-seven percent of patients with lower extremity bites were not wearing shoes. Common tissue findings associated with envenomation were swelling, ecchymosis, and erythema. Systemic effects and hematologic toxicity were more common in rattlesnake than copperhead or cottonmouth envenomations. Crotalidae Polyvalent Immune Fab antivenom was given to 84% of patients. Twelve patients (4.3%) were re-admitted to the hospital after completion of treatment. Eight were re-treated with antivenom. The NASBR gathers detailed data on venomous snakebites across the US. In its initial years, useful information has already been gained. Data regarding footwear will inform public health interventions and education, and information regarding the clinical presentation may help physicians better anticipate effects and manage snakebite. As the number of cases in the NASBR grows, associations between patient-related factors and outcomes may be studied.

Introduction: In the developing world, occupation has been identified as a risk factor for snake bite. Such an association has not been described in the USA. The objective of this study was to describe the epidemiology and clinical manifestations of occupational snake bite in patients reported to the ToxIC North American Snakebite Registry (NASBR)., Methods: This was a prospective case series of patients reported to the ToxIC NASBR between January 1, 2014 and November 5, 2015. Variables collected included snake species, patient demographics, date and location of exposure, occupation, bite location, clinical manifestations, and management., Results: Of 180 adult snake bites reported, 25 (13.9 %; 95 % CI 9.2-19.8 %) were occupational in nature. Rattlesnake envenomations were common (80 %). Most snake bites (96 %) occurred in men. Occupations most associated with snake bite were landscaping (28 %) and working directly with snakes (24 %). Fifty-six percent of bites occurred in an outdoor work environment. Seventy-six percent of envenomations were to the upper extremities. Intentional interaction occurred in 40 % of cases, all of which sustained finger envenomations. No cases presented with apparent acute ethanol intoxication., Conclusions: The majority of occupational snake bites occurred in men working outdoors and were unintentional injuries. Bites involving the upper extremity tended to result from intentional interactions. Acute ethanol intoxication did not appear to be involved with occupational envenomations., Competing Interests: Compliance with Ethical Standards Conflicts of Interest Authors Meghan Spyres MD, Anne-Michelle Ruha MD, Steven Seifert MD, Nancy Onisko DO, Angela Padilla-Jones RN, and Eric Smith MSIS have no conflicts of interest to declare. Funding There was no direct funding for this project. BTG International sponsored an unrestricted grant to ACMT for the NASBR registry.

Background: Crotalidae Polyvalent Immune Fab (Ovine) has been the only antivenom commercially available in the US since 2007 for treatment of Crotalinae envenomation. Late coagulopathy can occur or recur after clearance of Fab antivenom, often after hospital discharge, lasting in some cases more than 2 weeks. There have been serious, even fatal, bleeding complications associated with recurrence phenomena. Frequent follow-up is required, and additional intervention or hospitalization is often necessary. F(ab')2 immunoglobulin derivatives have longer plasma half life than do Fab. We hypothesized that F(ab')2 antivenom would be superior to Fab in the prevention of late coagulopathy following treatment of patients with Crotalinae envenomation., Methods: We conducted a prospective, double-blind, randomized clinical trial, comparing late coagulopathy in snakebitten patients treated with F(ab')2 with maintenance doses [F(ab')2/F(ab')2], or F(ab')2 with placebo maintenance doses [F(ab')2/placebo], versus Fab with maintenance doses [Fab/Fab]. The primary efficacy endpoint was coagulopathy (platelet count < 150 K/mm(3), fibrinogen level < 150 mg/dL) between end of maintenance dosing and day 8., Results: 121 patients were randomized at 18 clinical sites and received at least one dose of study drug. 114 completed the study. Of these, 11/37 (29.7%) in the Fab/Fab cohort experienced late coagulopathy versus 4/39 (10.3%, p < 0.05) in the F(ab')2/F(ab')2 cohort and 2/38 (5.3%, p < 0.05) in the F(ab')2/placebo cohort. The lowest heterologous protein exposure was with F(ab')2/placebo. No serious adverse events were related to study drug. In each study arm, one patient experienced an acute serum reaction and one experienced serum sickness., Conclusions: In this study, management of coagulopathic Crotalinae envenomation with longer-half-life F(ab')2 antivenom, with or without maintenance dosing, reduced the risk of subacute coagulopathy and bleeding following treatment of envenomation.

Introduction: The technology of antivenom production has gradually changed since the earliest production of antisera around the turn of the 20th century. Use of early antisera was associated with frequent acute adverse reactions and serum sickness. New F(ab')2 products, manufactured using pepsin degradation of immunoglobulin together with precipitation of unwanted protein and albumin serum fractions, should in concept cause fewer immune reactions in clinical use., Methods: A linked set of five prospective clinical trials of an equine F(ab')2 antivenom, together with one historical control study, were completed during development of the product for a Biological License Application through the US FDA. Adverse events were recorded and categorized, with particular attention to the frequency of immune reactions., Results: A total of 1534 patients ages 0.1-90.5 years received antivenom, in Arizona and in Mexico, for treatment of scorpion envenomation. Total dosing ranged from 1 to 5 vials except for one outlier who received 10 vials. Estimated protein exposure was 12-275 mg per patient (outlier, up to 550 mg). Three patients (0.2%) had acute reactions to antivenom infusion (one urticaria, one urticaria and dyspnea, and one panic attack). Eight (0.5%) had rashes suggestive of Type 3 immune reactions, although none had the full syndrome of serum sickness. Two women were treated for envenomation during the first trimester of pregnancy, one of whom subsequently experienced a spontaneous abortion., Conclusions: Rates of immune reaction to this product were two orders of magnitude lower than the range (up to 75% for early and 81% for late reactions) historically reported with use of minimally refined whole immunoglobulin products against a variety of infections and envenomations. Lower protein dose, greater purity of the active component, lack of the immunogenic Fc portion of the immunoglobulin molecule, and slow intravenous infusion are likely to be the reason for this. Clinical implications of a safer product include that it can be employed in settings where antivenom was once considered too dangerous to use, such as primary care clinics and remote rural areas., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Study Objective: Ethylene glycol remains an important toxic cause of metabolic acidosis and acute renal failure. Traditionally, inhibition of alcohol dehydrogenase along with hemodialysis has been used for treatment. Because of reported long elimination half-life of ethylene glycol during alcohol dehydrogenase inhibition, hemodialysis has been used in patients who are otherwise doing well to clear ethylene glycol. We study ethylene glycol elimination kinetics in patients treated with fomepizole, but without hemodialysis., Methods: This was a retrospective, multicenter cohort study of patients older than 15 years who were treated at one of 3 medical centers during an 8-year period. Inclusion criteria were peak serum ethylene glycol concentration greater than 20 mg/dL, lack of renal failure on admission, treatment with fomepizole but without hemodialysis, and availability of serial serum ethylene glycol concentrations, allowing calculation of elimination half-life. The primary outcome variable was ethylene glycol elimination half-life; mortality and onset of renal failure were secondary outcome variables., Results: During the study period, 85 patients were treated for ethylene glycol toxicity, of whom 40 met inclusion criteria. The mean serum ethylene glycol elimination half-life was 14.2 hours (SD=3.7 hours; 95% confidence interval 13.1 to 15.3 hours). One patient presented with metabolic acidosis on admission and developed mild transient renal insufficiency but did not require hemodialysis. No patient died., Conclusion: The mean elimination half-life of ethylene glycol in this population was shorter than previously reported without hemodialysis, and this select group of patients did well without enhanced elimination by hemodialysis., (Copyright © 2012. Published by Mosby, Inc.)

Background: Envenomation by crotaline snakes (rattlesnake, cottonmouth, copperhead) is a complex, potentially lethal condition affecting thousands of people in the United States each year. Treatment of crotaline envenomation is not standardized, and significant variation in practice exists., Methods: A geographically diverse panel of experts was convened for the purpose of deriving an evidence-informed unified treatment algorithm. Research staff analyzed the extant medical literature and performed targeted analyses of existing databases to inform specific clinical decisions. A trained external facilitator used modified Delphi and structured consensus methodology to achieve consensus on the final treatment algorithm., Results: A unified treatment algorithm was produced and endorsed by all nine expert panel members. This algorithm provides guidance about clinical and laboratory observations, indications for and dosing of antivenom, adjunctive therapies, post-stabilization care, and management of complications from envenomation and therapy., Conclusions: Clinical manifestations and ideal treatment of crotaline snakebite differ greatly, and can result in severe complications. Using a modified Delphi method, we provide evidence-informed treatment guidelines in an attempt to reduce variation in care and possibly improve clinical outcomes.

Background: North American rattlesnake envenomations commonly produce defibrination, coagulopathy and/or thrombocytopenia, which may be reversed following treatment with Crotalidae Polyvalent Immune Fab Ovine (FabAV). Despite initial resolution with FabAV, late onset or recurrence of venom-induced hematologic effects may occur. Time at which onset of late hematotoxicity may first be detected is unknown. The purpose of this study was to identify the incidence and time of onset of recurrent or new late hypofibrinogenemia, coagulopathy, or thrombocytopenia in a cohort of rattlesnake envenomation patients seen in outpatient follow-up after treatment with FabAV, and to report hematologic outcomes in these patients., Methods: Review of 66 charts of patients with rattlesnake envenomation who were treated with FabAV, and subsequently had outpatient follow-up evaluation at least 48 h after last FabAV, was performed. Demographic information, rattlesnake and bite characteristics, dose and timing of antivenom administration, adverse events, in-patient laboratory values, length of hospital stay, and follow-up laboratory values were collected. The primary outcome parameters were recurrent or delayed onset coagulopathy, hypofibrinogenemia, or thrombocytopenia identified no sooner than 48 h after last dose of FabAV., Results: Prior to control of the envenomation with FabAV, 42 patients (63.6%) experienced hematologic toxicity. At follow-up, 21 patients (32%) were found to have late coagulopathy, hypofibrinogenemia, or thrombocytopenia. Of twenty-three patients (35%) with more than one follow-up visit, fifteen had normal laboratory findings at the first follow-up visit. Five of these 15 patients (8% of total study group; 33% of this subgroup) with normal hematologic studies at first follow-up exhibited late hematologic toxicity at second follow-up. Severe late hematologic toxicity developed in five of 66 (8%) patients. One patient was retreated with FabAV for late severe thrombocytopenia., Conclusion: Recurrent and delayed onset of hematologic toxicity in rattlesnake envenomation victims treated with FabAV is common. Follow-up more than three days after treatment is necessary to detect all cases of late hematologic toxicity., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Latrodectus envenomations are common throughout the United States and the world. While many envenomations can result in catecholamine release with resultant hypertension and tachycardia, myocarditis is very rare. We describe a case of a 22-year-old male who sustained a Latrodectus envenomation complicated by cardiomyopathy.

A 39-year-old woman intentionally ingested Amberes shoe dye containing both methanol and aniline. She subsequently developed life-threatening methanol poisoning, methemoglobinemia, hemolytic anemia, and sulfhemoglobinemia. Treatment involved methylene blue infusion, emergent hemodialysis, fomepizole therapy, and blood products. Multiple toxicities can occur after ingestion of shoe dyes.

Objective: To determine whether intravenous (IV) hypertonic sodium bicarbonate is effective in the reversal of QRS widening associated with severe Taxus intoxication., Methods: Seventeen anesthetized and instrumented swine were poisoned with an IV extract of Taxus media until doubling of the QRS interval on electrocardiography was achieved. After poisoning (time zero), the animals received either 4 mL/kg IV 8.4% sodium bicarbonate (experimental group; 6 animals), a similar volume of 0.7% NaCl in 10% mannitol (mannitol group; 6 animals), or nothing (control group; 5 animals). The main outcome parameter was QRS duration. Secondary outcome parameters were mean arterial pressure (MAP), heart rate (HR), and cardiac index (CI = cardiac output/kg). Additionally, arterial pH, partial pressure of carbon dioxide (pCO(2)), and plasma-ionized calcium, sodium, and potassium were monitored., Results: Taxus toxicity, defined as a 100% increase in QRS duration, was produced in all animals. The animals were similar in regard to baseline and time 0 physiologic parameters as well as amount of Taxus media extract administered. From times 5 through 30 minutes, following assigned treatment, significant increases in QRS duration were detected in the experimental and mannitol groups compared with the control group. A significant lowering of MAP was found in the experimental group compared with the control group. No significant difference between groups was noted in HR or CI. The swine treated with hypertonic sodium bicarbonate had a statistically significant increase in pH, plasma sodium concentration, and base excess compared with the other groups., Conclusions: Hypertonic sodium bicarbonate was ineffective in reversing the widening of QRS interval associated with Taxus poisoning in this swine model.