A ten-year retrospective California Poison Control System experience with possible amatoxin mushroom calls.

INTRODUCTION: Mushrooms containing amatoxin are found worldwide and represent a challenging poisoning for the clinician and consulting poison center. This study evaluates the experience of a large poison system with possible amatoxin-containing mushroom ingestion calls. METHODS: A 10-year retrospective review of the California Poison Control System database was performed for amatoxin mushroom ingestion calls resulting in hospitalization. Cases found were abstracted and data statistically analyzed for association with a composite endpoint of death, liver transplant, and/or the need for dialysis. RESULTS: Amatoxin-containing mushroom calls are infrequent with the vast majority (98.4 percent) coming from Northern California during the rainier first and fourth quarters (October through March) of the year. Elevated initial aminotransferase activities and international normalized ratios were predictive of the composite negative outcome. The mortality plus liver transplant and hemodialysis composite rate was 8.2 percent, consistent with current literature. CONCLUSION: The California Poison Control System has relatively few amatoxin-containing mushroom ingestion calls that result in hospitalization but those that are reported mostly occur in Northern California. Treatment bias towards the sickest patients may explain the association of intravenous fluid use or treatment with acetylcysteine or silibinin with meeting the composite outcome. The initial presence of elevated hepatic aminotransferase activity and international normalized ratios are poor prognostic indicators and are likely reflective of late presentation, an advanced toxic phase of amatoxin poisoning, and/or delays in time to obtain poison center consultation.

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.

Buprenorphine for High-dose Tramadol Dependence: A Case Report of Successful Outpatient Treatment.

INTRODUCTION: During the coronavirus disease 2019 pandemic caused by the severe acute respiratory syndrome coronavirus 2, deaths from opiate drug overdoses reached their highest recorded annual levels in 2020. Medication-assisted treatment for opiate use disorder has demonstrated efficacy in reducing opiate overdoses and all-cause mortality and improving multiple other patient-centered outcomes. Treatment of tramadol dependence in particular poses unique challenges due to its combined action as opioid agonist and serotonin-norepinephrine reuptake inhibitor. Tramadol puts patients with dependence at risk for atypical withdrawal syndromes when attempting to reduce use. Little evidence is available to guide treatment of tramadol dependence. CASE REPORT: We present a case of high-dose tramadol addiction that began with misuse of medically prescribed tramadol for treatment of musculoskeletal back pain. The patient's use reached oral consumption of 5000-6000 milligrams of illicit tramadol daily. She complained of common complications of tramadol use disorder including memory impairment, excessive sedation, and tramadol-induced seizures. The patient was referred to the emergency department in a withdrawal crisis seeking treatment where she was successfully managed with buprenorphine and phenobarbital and then linked to ongoing outpatient treatment. CONCLUSION: Our report adds to the limited guidance currently available on the acute management of tramadol withdrawal and treatment of tramadol use disorder. Our case suggests the initiation of high-dose buprenorphine may be an effective and feasible option for emergency clinicians.

Severe Methemoglobinemia and Death From Intentional Sodium Nitrite Ingestions.

BACKGROUND: Sodium nitrite is known to induce methemoglobinemia and hypotension when ingested, but reports of intentional ingestion remain rare. CASE SERIES: We report five cases of severe methemoglobinemia secondary to large sodium nitrite ingestion that were reported to and managed by the California Poison Control System in 2019, resulting in three fatalities. The estimated doses ingested ranged from 15 grams to 113 grams, with one patient surviving after an ingestion of 60 grams. The highest documented methemoglobin level was 73%. The 2 patients who survived received methylene blue early in their clinical course. One patient required higher doses of methylene blue compared with other cases of nitrite-associated methemoglobinemia. In the patients who survived, all symptoms resolved within 24 h. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: These cases highlight the severe toxicity associated with intentional large sodium nitrite ingestion. In management, consideration should be given to administering higher initial or more frequent doses of methylene blue compared with standard practice. Given that sodium nitrite is readily accessible through online vendors, and is being circulated through various suicide forums, it has the potential to be more commonly encountered in the emergency department.

The Global Educational Toxicology Toolkit (GETKIT): A 1-Day Course for Teaching Poisoning Essentials in Low- and Middle-Income Countries (LMIC): Course Development and Pilot Data Analysis.

INTRODUCTION: Worldwide an estimated one million deaths occur annually as a result of poisoning. Internationally there is a lack of toxicology training programs, especially in resource poor settings. We developed a one-day, interactive toxicology curriculum for healthcare practitioners in countries lacking clinical toxicology training and evaluated its feasibility and effectiveness for knowledge dissemination. METHODS: GETKIT was developed with 3 sections: didactics, hands on toxicology case lab, and technology clinic. The investigators, who are medical toxicologists,created 23 didactic lectures and 42 workshop cases. All materials were peer reviewed by 5 senior medical toxicologists for content validity. Participants atpilot sites were given pre-course, post-course, and 3-month follow-up tests and surveys. RESULTS: GETKIT was delivered internationally at 7 sites between November 2017 and April 2018. There were 186 total participants. One hundred and ten participants (59%) reported their hospital lacked a clinical toxicology service. The median post course score 12 (60%), IQR (6,14) was significantly higher compared to the pre-course score 9 (45%), IQR (6,11) (p < 0.0001). There was a significantly higher median 3-month post course score 13 (65%), IQR (8,14) vs. a median pre course score of 9 (45%), IQR (6,11) (p 0.0005). At 3-month follow up 86% of participants reported GETKIT had changed their clinical practice. CONCLUSIONS: An improvement in and retention of medical toxicology knowledge was demonstrated with the GETKIT course. It also conferred improvement in selfreportedpoisoning management practices in participants from low resource settings.

Exposures to Single-Use Detergent Sacs Reported to a Statewide Poison Control System, 2013-2015.

BACKGROUND: Single-use detergent sacs (SUDSs) represent a relatively new household hazard to children. Brand differences and packaging changes may contribute to differential risks with accidental exposure. We sought to identify high-risk features from SUDS exposures in children and to assess whether product packaging changed trends in SUDS exposures reported to poison centers. METHODS: In this institutional review board-approved, retrospective chart review of SUDS exposures from January 2013 to August 2015, deidentified case records of a large statewide poison control system were extracted and analyzed for clinical associations and trends. Clinical and demographic data were gathered, and outcomes were analyzed for differences by brand type, presenting complaints, and occurrence in relation to SUDS packaging changes. RESULTS: There were 3502 SUDS exposures, with 3343 (95%) in children 5 years or younger. Metabolic, central nervous system, and pulmonary effects were significantly associated with moderate or severe outcome (P < 0.05). Forty patients received invasive procedures such as endoscopy, bronchoscopy, and/or endotracheal intubation, and more than half had mucosal lesions discovered by the diagnostic procedure. The presence of stridor, wheezing, drooling, lethargy, and exposure to the brand All Mighty Pacs were all significant predictors of moderate or severe outcome (P < 0.05). After the implementation of packaging changes, there was a transient decline in the number of exposures to the Tide Pods product. CONCLUSION: Central nervous system and respiratory effects as well as certain brand types predict serious outcomes from SUDS exposures. Manufacturing changes had a brief beneficial effect on the volume of SUDS exposures reported between 2013 and 2015.

Cardiac Toxicity from Intentional Ingestion of Pong-Pong Seeds (Cerbera Odollam).

BACKGROUND: A variety of plants contain cardiac glycosides. This has resulted in many of them being used to commit suicide. In southeast Asia, Cerebera odollam (pong-pong or suicide tree) is frequently used for suicidal ingestion. Seeds, or kernels, of this plant can cause hyperkalemia, heart block, and death due to the effects of its cardiac glycosides. CASE REPORT: We describe six cases of pong-pong seed ingestion reported to US poison centers. The most common symptoms were vomiting and bradycardia. Three patients survived and three died. All patients who died had heart block, serum digoxin levels > 1.0 ng/mL, and were treated with anti-digoxin immune FAB. Anti-digoxin immune FAB may be ineffective in a large pong-pong seed ingestion. Patients ingesting pong-pong seeds who develop a potassium level > 8.0 meq/L or have a digoxin level > 1.0 ng/mL may be at a higher risk for death. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The apparent ease of acquiring C. odollam seeds on the Internet makes knowledge of it important, as it can be used as a means to commit suicide. The apparent failure of digoxin immune FAB to treat toxicity from pong-pong is important, as other lifesaving techniques, such as extracorporeal membrane oxygenation, might be needed in severely toxic patients.

Assessing the Effect of a Medical Toxicologist in the Care of Rattlesnake-envenomated Patients.

BACKGROUND: Rattlesnake envenomation is an important problem in the United States, and the management of these envenomations can be complex. Despite these complexities, however, the majority of such cases are managed without the involvement of a medical toxicologist. The primary objective of this study was to evaluate the impact of a medical toxicology service (MTS) on the length of stay (LOS) of such patients. METHODS: The authors conducted a retrospective study at six centers in California. Patients were included if they were admitted in the 2 years before the establishment of a MTS (pre-MTS) or in the 2 years after the creation of a MTS (post-MTS). RESULTS: A total of 300 subjects were included (169 pre-MTS, 131 post MTS). Baseline characteristics between the pre-MTS and post-MTS groups were very similar. The creation of a MTS was associated with a significant reduction in the mean (95% confidence interval) LOS (69.5 [59.1-79.9] hours vs. 48.1 [41.4-54.8] hours). This reduced LOS was not associated with any statistically significant change in readmission rates. CONCLUSION: Rattlesnake bite patients treated by a medical toxicologist have a significantly reduced LOS compared to those without direct involvement of a medical toxicologist.

Epidemiology and clinical outcomes of snakebite in the elderly: a ToxIC database study.

INTRODUCTION: Epidemiologic studies of snakebites in the United States report typical victims to be young men. Little is known regarding other demographics including children and the elderly. The objective of this study was to describe the epidemiology and clinical manifestations of snake bite in elderly patients reported to the ToxIC (Toxicology Investigators Consortium) North American Snakebite Registry (NASBR) Methods: This was a multicenter analysis of a prospectively collected cohort of patients with snakebite reported to the ToxIC NASBR between 1 January 2013 and 31 December 2015. Inclusion criterion was age >65. Variables collected included patient demographics, medical comorbidities, medications, date the case was reported to the registry, location of exposure, bite location, snake species, clinical manifestations, outcomes, and management. RESULTS: Of the 450 cases reported, 30 (6.7%) occurred in elderly patients, with an average age of 74 years. Rattlesnake envenomations were common (93.3%). The majority of patients were men (66.7%) and reported at least one medical comorbidity (83.3%). Most patients were on cardiac medications (60%) and use of antiplatelet or anticoagulant medications was common (33%). Hemotoxicity occurred in 30% of patients on initial presentation and 11.5% of patients on initial follow-up. No clinically significant early or late bleeding was observed. CONCLUSIONS: Elderly patients with North American snake envenomation are likely to have co-morbidities and to take medications that may increase their risk for hemotoxicity, however risk of bleeding or other complications was not increased in this group.

Pediatric Exposures to Topical Benzocaine Preparations Reported to a Statewide Poison Control System.

INTRODUCTION: Topical benzocaine is a local anesthetic commonly used to relieve pain caused by teething, periodontal irritation, burns, wounds, and insect bites. Oral preparations may contain benzocaine concentrations ranging from 7.5% to 20%. Pediatric exposure to such large concentrations may result in methemoglobinemia and secondarily cause anemia, cyanosis, and hypoxia. METHODS: This is a retrospective study of exposures reported to a statewide poison control system. The electronic health records were queried for pediatric exposures to topical benzocaine treated at a healthcare facility from 2004 to 2014. Cases of benzocaine exposure were reviewed for demographic and clinical information, and descriptive statistical analysis was performed. RESULTS: The query resulted in 157 cases; 58 were excluded due to co-ingestants, or miscoding of non-benzocaine exposures. Children four years of age and younger represented the majority of cases (93%) with a median age of 1 year. There were 88 cases of accidental/ exploratory exposure, while 6 cases resulted from therapeutic application or error, 4 cases from adverse reactions, and 1 case from an unknown cause. Asymptomatic children accounted for 75.5% of cases, but major clinical effects were observed in 5 patients. Those with serious effects were exposed to a range of benzocaine concentrations (7.5-20%), with 4 cases reporting methemoglobin levels between 20.2%-55%. Methylene blue was administered in 4 of the cases exhibiting major effects. CONCLUSION: The majority of exposures were accidental ingestions by young children. Most exposures resulted in minor to no effects. However, some patients required treatment with methylene blue and admission to a critical care unit. Therapeutic application by parents or caregivers may lead to adverse effects from these commonly available products.

Impact of online toxicology training on health professionals: the Global Educational Toxicology Uniting Project (GETUP).

OBJECTIVE: The Global Educational Toxicology Uniting Project (GETUP), supported by the American College of Medical Toxicology, links countries with and without toxicology services via distance education with the aim to improve education. Due to the lack of toxicology services in some countries there is a knowledge gap in the management of poisonings. We describe our experience with the worldwide delivery of an online introductory toxicology curriculum to emergency doctors and other health professionals treating poisoned patients. METHODS: We delivered a 15-module introductory Internet-based toxicology curriculum to emergency doctors and health professionals, conducted from August to December 2016. This Internet-based curriculum was adapted from one used to teach emergency residents toxicology in the United States. Modules covered themes such as pharmaceutical (n = 8), toxidromes (n = 2) and agrochemicals (n = 5) poisoning. Participants completed pre-test and post-test multiple choice questions (MCQs) before and after completing the online module, respectively, throughout the course. We collected information on participant demographics, education and training, and perception of relevance of the curriculum. Participants gave feedback on the course and how it affected their practice. RESULTS: One hundred and thirty-six health professionals from 33 countries participated in the course: 98 emergency doctors/medical officers, 25 physicians, eight pharmacists/poisons information specialists, two toxicologists, two medical students and one nurse. Median age of participants was 34 years. Median number of years postgraduate was seven. Ninety (65%) had access to either a poisons information centre over the phone or toxicologist and 48 (35%) did not. All participants expected the course to help improve their knowledge. Overall median pre-module MCQ scores were 56% (95%CI: 38, 75%) compared to post-module MCQ scores median 89% (95% CI: 67, 100%) (p < .0001). CONCLUSIONS: Our participants demonstrated an increase in medical knowledge based on performance on MCQs. An online toxicology curriculum is an effective way to deliver education to health professionals treating poisoned patients and can help to bridge the knowledge gap and change practice in developed and developing countries.

Estimating the impact of adopting the revised United Kingdom acetaminophen treatment nomogram in the U.S. population.

BACKGROUND: Acetaminophen toxicity is common in clinical practice. In recent years, several European countries have lowered the treatment threshold, which has resulted in increased number of patients being treated at a questionable clinical benefit. OBJECTIVE: The primary objective of this study is to estimate the cost and associated burden to the United States (U.S.) healthcare system, if such a change were adopted in the U.S. METHODS: This study is a retrospective review of all patients age 14 years or older who were admitted to one of eight different hospitals located throughout the U.S. with acetaminophen exposures during a five and a half year span, encompassing from 1 January 2008 to 30 June 2013. Those patients who would be treated with the revised nomogram, but not the current nomogram were included. The cost of such treatment was extrapolated to a national level. RESULTS: 139 subjects were identified who would be treated with the revised nomogram, but not the current nomogram. Extrapolating these numbers nationally, an additional 4507 (95%CI 3641-8751) Americans would be treated annually for acetaminophen toxicity. The cost of lowering the treatment threshold is estimated to be $45 million (95%CI 36,400,000-87,500,000) annually. CONCLUSIONS: Adopting the revised treatment threshold in the U.S. would result in a significant cost, yet provide an unclear clinical benefit.

Analysis of Gastric Lavage Reported to a Statewide Poison Control System.

BACKGROUND: As decontamination trends have evolved, gastric lavage (GL) has become a rare procedure. The current information regarding use, outcomes, and complications of GL could help refine indications for this invasive procedure. OBJECTIVES: We sought to determine case type, location, and complications of GL cases reported to a statewide poison control system. METHODS: This is a retrospective review of the California Poison Control System (CPCS) records from 2009 to 2012. Specific substances ingested, results and complications of GL, referring hospital ZIP codes, and outcomes were examined. RESULTS: Nine hundred twenty-three patients who underwent GL were included in the final analysis, ranging in age from 9 months to 88 years. There were 381 single and 540 multiple substance ingestions, with pill fragment return in 27%. Five hundred thirty-six GLs were performed with CPCS recommendation, while 387 were performed without. Complications were reported for 20 cases. There were 5 deaths, all after multiple ingestions. Among survivors, 37% were released from the emergency department, 13% were admitted to hospital wards, and 48% were admitted to intensive care units. The most commonly ingested substances were nontricyclic antidepressant psychotropics (n = 313), benzodiazepines (n = 233), acetaminophen (n = 191), nonsteroidal anti-inflammatory drugs (n = 107), diphenhydramine (n = 70), tricyclic antidepressants (n = 45), aspirin (n = 45), lithium (n = 36), and antifreeze (n = 10). The geographic distribution was clustered near regions of high population density, with a few exceptions. CONCLUSIONS: Toxic agents for which GL was performed reflected a broad spectrum of potential hazards, some of which are not life-threatening or have effective treatments. Continuing emergency physician and poison center staff education is required to assist in patient selection.

A season of snakebite envenomation: presentation patterns, timing of care, anti-venom use, and case fatality rates from a hospital of southcentral Nepal.

Snakebite envenomation affects thousands of people annually in Nepal. Published hospital-based studies of snakebite treatment in Nepal are scarce. Here we present the results of the first prospective, cross-sectional study of hospitalized envenomed snakebite cases in southcentral Nepal, a region characterized by poor pre-hospital care of snakebites, limited supply and excessive use of antivenom, and a high case/fatality ratio. We seek to identify clinical management problems and suggest potential interventions to improve treatment of snakebites. Out of the 342 patients presented with snakebites to an urban emergency department in the Terai region of Nepal between April and September of 2007, 39 patients were enrolled based on development of ptosis or swelling of bitten body parts. We collected patient demographic information and documented circumstances of snakebite, prehospital care, hospital care, and development of complications. Among 39 envenomated patients admitted to Bharatpur Hospital enrolled in the study 34 (92%) exhibited features of clinically significant neurotoxicity and were treated with antivenom. Antivenom use ranged from 4 to 98 vials of Polyspecific Indian Antivenom per patient. Each of victims (n=34) received antivenom an average of 4.3 (median) ±0.73 (standard error of mean) hours after receiving the snakebite. The overall case fatality rate was 21%. Neurotoxicity developed up to 25.8hr after suspected elapid snakebites. This was not observed for viperid snake bites. No enrolled patients received any of the currently recommended first aid for snake bite. The prevalence of nocturnal elapid snake bites, the practice of inappropriate first aid measures and highly variable administration of antivenom were identified as major challenges to appropriate care in this study. To address these issues we suggest development of a comprehensive checklist for identification of snake species, management of envenomation, and an educational program which teaches proper care at all stages of snakebite treatment.

Human bromethalin exposures reported to a U.S. Statewide Poison Control System.

BACKGROUND: Bromethalin is an increasingly used alternative to long-acting anticoagulant and cholecalciferol rodenticides. There are few reports of human exposures, and no existing professional society guidelines on medical management of bromethalin ingestions. The aim of this retrospective data review is to characterize bromethalin exposures reported to the California Poison Control System (CPCS) between 1997 and 2014. METHODS: This is an observational retrospective case review of our statewide poison control system's electronic medical records. Following Institutional Board Review and Research Committee approvals, poison center exposures related to bromethalin were extracted using substance code and free text search strategies. Case notes of bromethalin exposures were reviewed for demographic, clinical, laboratory, and outcome information; inclusion criteria for the study was single-substance, human exposure to bromethalin. RESULTS: There were 129 calls related to human bromethalin exposures (three cases met exclusion criteria). The age range of cases was 7 months-90 years old, with the majority of exposures (89 cases; 70.6%), occurring in children younger than 5 years of age (median age of 2 years). Most exposures occurred in the pediatric population as a result of exploratory oral exposure. One hundred and thirteen patients (89.7%) had no effects post exposure, while 10 patients (7.9%) had a minor outcome. Adverse effects were minor, self-limited, and mostly gastrointestinal upset. There were no moderate, major, or fatal effects in our study population. The approximate ingested dose, available in six cases, ranged from 0.067 mg/kg to 0.3 mg/kg (milligrams of bromethalin ingested per kilogram of body weight), and no dose-symptom threshold could be established from this series. Exposures were not confirmed through urine or serum laboratory testing. DISCUSSION: The prognosis for most accidental ingestions appears to be excellent. However, bromethalin exposures may result in a higher number of symptomatic patients than long-acting anticoagulant agents. Parents, physicians and poison control specialists are encouraged to maintain a high index of suspicion for bromethalin-related complications in all cases of rodenticide exposures. CONCLUSIONS: Accidental bromethalin exposures in children appear to be self-limited in toxicity. Additional studies are warranted to determine whether more severe effects are precipitated when larger amounts are involved, particularly in suicidal ingestion.

The Global Educational Toxicology Uniting Project (GETUP): an Analysis of the First Year of a Novel Toxicology Education Project.

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.