Fomepizole as an Adjunctive Treatment in Severe Acetaminophen Toxicity.

A 33-year-old male presented to the emergency department with a chief complaint of abdominal pain after taking #50 500 mg acetaminophen tablets over the preceding two days. He was tachycardic and tachypneic, and the initial labs were notable for acetaminophen level, 337 mg/L; AST, 137 IU/L; ALT, 194 IU/L; ABG pH, 7.24; and lactate, 4.1 mmol/L. The patient was started on IV N-Acetylcysteine (NAC) as well as given a single dose of 15 mg/kg fomepizole. The patient did remarkably well, with a peak AST of 198 IU/L, peak ALT of 301 IU/L, and peak INR of 3.1. Biochemical and animal data support fomepizole having hepatoprotective effects in acetaminophen poisoning. To our knowledge, this is the first human case of an intentional dual NAC/fomepizole regimen for severe acetaminophen toxicity.

Assessing Bleeding Risk in Patients With Intentional Overdoses of Novel Antiplatelet and Anticoagulant Medications.

STUDY OBJECTIVE: In recent years, the use of novel anticoagulants and antiplatelet agents has become widespread. Little is known about the toxicity and bleeding risk of these agents after acute overdose. The primary objective of this study is to evaluate the relative risk of all bleeding and major bleeding in patients with acute overdose of novel antiplatelet and anticoagulant medications. METHODS: This study is a retrospective study of acute ingestion of apixaban, clopidogrel, ticlopidine, dabigatran, edoxaban, prasugrel, rivaroxaban, and ticagrelor reported to 7 poison control centers in 4 states during a 10-year span. The prevalence of bleeding for each agent was calculated, and hemorrhage was classified as trivial, minor, or major. RESULTS: A total of 322 acute overdoses were identified, with the majority of cases involving clopidogrel (260; 80.7%). Hemorrhage occurred in 16 cases (4.9%), including 7 cases of clopidogrel, 6 cases of rivaroxaban, 2 cases of dabigatran, and 1 case of apixaban. Most cases of hemorrhage were classified as major (n=9). Comparing the novel anticoagulants with the P2Y12 receptor inhibitors, the relative risk for any bleeding with novel anticoagulant was 6.68 (95% confidence interval 2.63 to 17.1); the relative risk of major bleeding was 18.1 (95% confidence interval 3.85 to 85.0). CONCLUSION: Acute overdose of novel anticoagulants or antiplatelet agents is associated with a small risk of significant hemorrhage. The risk is greater with the factor Xa inhibitors and direct thrombin inhibitors than with the P2Y12 receptor antagonists.

Photokeratitis among restaurant workers: A case series.

This case report highlights the challenges associated with the diagnosis and workplace evaluation of occupationally acquired ultraviolet (UV) radiation-induced photokeratitis and associated skin burns in a group of restaurant workers. UV-C spectrum bulbs were inadvertently shipped and installed in insect light traps. Ocular and dermal symptoms were reported in 18 of 85 restaurant employees to varying degrees of severity over a 2-day period. One patient was formally diagnosed with a chemical burn/irritation of the cornea. More severe symptoms were reported by individuals working in close proximity to the lights. This clinical picture can resemble mass chemical or irritant exposure when multiple individuals are affected, and a multidisciplinary approach was required for rapid identification of the source to limit morbidity. Prevention strategies for similar events should be considered which can include limiting hardware compatibility and improving warning labels.

Laundry detergent "pod" ingestions: a case series and discussion of recent literature.

OBJECTIVES: The objectives of this study were to present and explore the clinical presentation of the increasingly common pediatric exposure to the widely available single-use laundry packets or "laundry pods." METHODS: This is a case report of 4 pediatric patients with significant toxicity due to laundry pod detergent exposure and a review of the available literature including abstract-only publications. RESULTS: An unexpectedly severe clinical pattern was noted; 3 of the 4 children required intubation for management, airway injury was noted in 1 of them, and 2 of them had hospital courses of at least 1 week. The literature suggests that laundry pod exposures are associated with increased morbidity compared to traditional laundry detergent exposures. To date, no specific contaminant or component has been identified as being responsible for the injury, although some evidence points to the surfactant component. CONCLUSIONS: A different approach to the triage and management of pediatric exposures to laundry detergent pod ingestions is required compared with nonpod ingestions. Although the exact cause is not known, practitioners should be vigilant for rapid onset of neurological impairment and inability to protect the airway in addition to its caustic effects.

Evaluation of changes in poisoning in young children: 2000 to 2010.

OBJECTIVE: The nature of pediatric poisonings is dynamic, with changes occurring over time. We evaluated poisoning in children younger than 6 years for trends during an 11-year period regarding the substances involved in the poisoning, medical outcomes, and health care use. METHODS: This was retrospective study of poisoning in children younger than 6 years reported to 12 poison centers in 5 U.S. states for the years 2000 through 2010. Data abstracted included substance category involved in the exposure, age of patient, year of occurrence, location of patient management, and medical outcome. RESULTS: There were 2,577,036 poison exposures in children younger than 6 years, with a 12.4% increase from 210,270 poison exposures in 2000 to 236,425 poison exposures in 2010. There was a 33% increase (P < 0.05) in pharmaceutical related exposures in children younger than 6 years and a 2.8% decline in the number of nonpharmaceutical related exposures. Among those substance categories representing more than 1% of exposures, the only pharmaceutical showing decline was cough/cold preparations. There was a 53% increase in serious medical outcomes, including 119 deaths and a significant increase in health care facility use, primarily owing to pharmaceutical exposures. CONCLUSIONS: Poisoning in young children increasingly involves pharmaceuticals and is associated with an increased number of serious outcomes and children treated in a health care facility. We believe that these changes are related to increased availability of medications in the home and poison prevention education efforts should include a focus on the availability of these products to small children.

2022 Annual Report of the National Poison Data System® (NPDS) from America's Poison Centers®: 40th Annual Report.

INTRODUCTION: This is the 40th Annual Report of America's Poison Centers National Poison Data System (NPDS). As of 1 January, 2022, all 55 of the nation's poison centers (PCs) uploaded case data automatically to NPDS. The upload interval was 4.72 [4.40, 9.27] (median [25%, 75%]) minutes, effectuating a near real-time national exposure and information database and surveillance system. METHODS: We analyzed the case data tabulating specific indices from NPDS. The methodology was similar to that of previous years. Where changes were introduced, the differences are identified. Cases with medical outcomes of death were evaluated by a team of medical and clinical toxicologist reviewers using an ordinal scale of 1-6 to assess the Relative Contribution to Fatality (RCF) of the exposure. RESULTS: In 2022, 2,483,183 closed encounters were logged by NPDS: 2,064,875 human exposures, 50,381 animal exposures, 363,099 information requests, 4,790 human confirmed nonexposures, and 38 animal confirmed nonexposures. Total encounters showed a 12.9% decrease from 2021, and human exposure cases decreased by 0.771%, while health care facility (HCF) human exposure cases increased by 0.214%. All information requests decreased by 48.4%, medication identification (Drug ID) requests decreased by 21.2%, and medical information requests showed a 76.92% decrease, although these remain twice the median number before the COVID-19 pandemic. Drug Information requests showed a 52.4% decrease, due to declining COVID-19 vaccine calls to PCs but still comprised 5.55% of all information contacts. Human exposures with less serious outcomes have decreased 1.70% per year since 2008, while those with more serious outcomes (moderate, major or death) have increased 4.41% per year since 2000.Consistent with the previous year, the top 4 substance classes most frequently involved in all human exposures were analgesics (11.5%), household cleaning substances (7.23%), antidepressants (5.61%), and cosmetics/personal care products (5.23%). Antihistamines (4.81%) replaced sedatives/hypnotics/antipsychotics as the 5th substance class. As a class, analgesic exposures increased most rapidly, by 1,514 cases/year (3.26%/year) over the past 10 years for cases with more serious outcomes.The top 5 most common exposures in children age 5 years or less were household cleaning substances (10.3%), analgesics (9.54%), cosmetics/personal care products (9.49%), dietary supplements/herbals/homeopathic (6.65%), and foreign bodies/toys/miscellaneous (6.61%). NPDS documented 3,255 human exposures resulting in death; 2,622 (80.6%) of these were judged as related (RCF of 1-Undoubtedly responsible, 2-Probably responsible, or 3-Contributory). CONCLUSIONS: These data support the continued value of PC expertise and the need for specialized medical toxicology information to manage the increasing number of more serious exposures. Unintentional and intentional exposures continue to be a significant cause of morbidity and mortality in the US. The near real-time status of NPDS represents a national public health resource to collect and monitor US exposure cases and information requests. The continuing mission of NPDS is to provide a nationwide infrastructure for surveillance for all types of exposures (e.g., foreign body, infectious, venomous, chemical agent, or commercial product), and the identification and tracking of significant public health events. NPDS is a model system for the near real-time surveillance of national and global public health.

Management of Acetaminophen Poisoning in the US and Canada: A Consensus Statement.

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.

Single bag high dose intravenous N-acetylcysteine associated with decreased hepatotoxicity compared to triple bag intravenous N-acetylcysteine in high-risk acetaminophen ingestions.

INTRODUCTION: There is controversy that the triple bag intravenous (IV) N-acetylcysteine (NAC) regimen may be underdosing the sickest patients in its current, common usage. We hypothesize that a higher dose IV NAC regimen improves some outcomes. METHODS: We conducted a poison center based retrospective observational study from January 1, 2016 to December 31, 2017 comparing a single bag higher dose IV NAC regimen (150 mg/kg over 1 h, 15 mg/kg/hour) to the triple bag IV NAC regimen (150 mg/kg over 1 h, 12.5 mg/kg/hour for 4 h, 6.25 mg/kg/hour). In a high-risk population of patients with acetaminophen ingestion (defined as multiplication product ≥ 10,000 mg/L IU/L, not acute ingestions receiving NAC within 8 h, and not hepatotoxic on first contact), we evaluated the rate of hepatotoxicity, peak transaminase, and rate of laboratory coagulopathy. RESULTS: 89 patients met the inclusion criteria. 12 of the 23 patients (52%) who received triple bag NAC became hepatotoxic and 10 (43%) became coagulopathic, while only 19 of 66 patients (29%) who received single bag NAC became hepatotoxic and 15 (23%) became coagulopathic; p = .043 and .057, resp. Mean peak transaminase was 4481 IU/L vs 2143 IU/L in those receiving triple bag NAC vs single bag NAC, difference of means 2338 IU/L; p = .026. CONCLUSION: In this exploratory study of a high-risk population of patients with acetaminophen ingestions, the single bag IV NAC regimen was associated with lower peak transaminase and fewer patients becoming hepatotoxic as compared to the triple bag IV NAC regimen.

Melatonin Supplementation in Undetermined Pediatric Deaths.

Since 2015, the North Carolina Office of the Chief Medical Examiner has investigated seven deaths of infants and toddlers, aged 2 months to 3 years, with exogenous melatonin detected upon toxicological analysis. Melatonin concentrations ranged from 3 to 1,400 ng/mL in postmortem whole blood. While the cause and the manner of all seven deaths were classified as undetermined, the analytical findings are noteworthy. Melatonin is generally considered a safe, natural product appearing in many over-the-counter supplements geared toward young children to facilitate calmness and improve sleep. Melatonin is a neurohormone, which regulates not only circadian rhythms and natural sleep but also other physiological functions. Endogenous melatonin production, derived from essential amino acid metabolism, does not begin until pineal gland maturation at ∼3 months of age with concentrations in plasma peaking during periods of darkness at ∼0.2 ng/mL. Administering commercially available melatonin supplements to infants results in levels substantially greater than endogenous sources, which should not be assumed to be safe just because of their endogenous nature. The finding of exogenous concentrations in some postmortem pediatric cases warrants attention. Several topics of interest surrounding these postmortem melatonin findings will be considered, such as minimal regulatory control over commercial products as well as the potential impact on hazardous sleeping conditions. This manuscript will outline the physiological effects of melatonin and detail the case studies from the North Carolina medical examiner system. Forensic toxicology laboratories should consider including melatonin at exogenous concentrations in their testing schemes for appropriate postmortem infant and toddler cases.

Adverse effects associated with bupropion therapeutic errors in adults reported to four United States Poison Centers.

CONTEXT: Bupropion is a frequently used medication. Excessive doses may cause altered mental status, seizures, and dysrhythmias. There is a need for accurate estimate of seizure risk with therapeutic errors and determination if minor symptoms are harbingers of more severe effects. METHODS: A retrospective review of adult, acute, unintentional therapeutic error, single substance bupropion ingestions with known outcome reported to four poison centers from January 1, 2004 to December 31, 2016. Data included age, gender, single error dose, total bupropion dose over 18 h, prior history of seizure, management site, observation time, occurrence of an out-of-hospital adverse event, "jittery"/anxious/agitated, tachycardia/palpitations, seizures, and dysrhythmias. We recorded the total bupropion dose over 18 h if known; otherwise, we used the single error dose. We compared means for parametric data. We used Fisher's exact test and Mann-Whitney for nonparametric data. RESULTS: We identified 754 potential cases, of which 637 met inclusion criteria after case review. Median age was 42 years, and 76.1% were female. Cases were predominantly managed at home (56.2%). Outcomes were no effect (50.1%), minor (45.5%) and moderate (4.4%). The reported dose with no effect/minor outcome was 694 (±297) mg, and for moderate outcome was 1250 (±815) mg (p < 0.0001). Seizures occurred in four patients with median onset time of 7 h [range 2-21.5 h]. The median reported dose in patients who seized was 900 mg [range 600-3000 mg]. Of patients who developed a seizure and/or an out-of-hospital adverse event, 83% were "jittery"/anxious/agitated whereas "jittery"/anxious/agitated was present in 27% of cases that did not (p = 0.008). Tachycardia/palpitations was reported in 12% of cases; more serious dysrhythmias were not reported. CONCLUSIONS: Outcomes from single unintentional ingestions of bupropion in adults are overall mild and appear to be dose related. Home management may be an option with doses up to 900 mg in an appropriate patient population.

2021 Annual Report of the National Poison Data System© (NPDS) from America's Poison Centers: 39th Annual Report.

ABSTRACTINTRODUCTION: This is the 39th Annual Report of America's Poison Centers' National Poison Data System (NPDS). As of 1 January, 2021, all 55 of the nation's poison centers (PCs) uploaded case data automatically to NPDS. The upload interval was 4.87 [4.38, 8.62] (median [25%, 75%]) minutes, effectuating a near real-time national exposure and information database and surveillance system. METHODS: We analyzed the case data tabulating specific indices from NPDS. The methodology was similar to that of previous years. Where changes were introduced, the differences are identified. Cases with medical outcomes of death were evaluated by a team of medical and clinical toxicologist reviewers using an ordinal scale of 1-6 to assess the Relative Contribution to Fatality (RCF) of the exposure. RESULTS: In 2021, 2,851,166 closed encounters were logged by NPDS: 2,080,917 human exposures, 62,189 animal exposures, 703,086 information requests, 4,920 human confirmed nonexposures, and 54 animal confirmed nonexposures. Total encounters showed a 14.0% decrease from 2020, and human exposure cases decreased by 2.22%, while health care facility (HCF) human exposure cases increased by 7.20%. All information requests decreased by 37.0%, medication identification (Drug ID) requests decreased by 20.8%, and medical information requests showed a 61.1% decrease, although these remain about 13-fold higher than before the COVID-19 pandemic. Drug Information requests showed a 146% increase, reflecting COVID-19 vaccine calls to PCs. Human exposures with less serious outcomes have decreased 1.80% per year since 2008, while those with more serious outcomes (moderate, major or death) have increased 4.56% per year since 2000.Consistent with the previous year, the top 5 substance classes most frequently involved in all human exposures were analgesics (11.2%), household cleaning substances (7.49%), cosmetics/personal care products (5.88%), antidepressants (5.61%), and sedatives/hypnotics/antipsychotics (4.73%). As a class, antidepressant exposures increased most rapidly, by 1,663 cases/year (5.30%/year) over the past 10 years for cases with more serious outcomes.The top 5 most common exposures in children age 5 years or less were cosmetics/personal care products (10.8%), household cleaning substances (10.7%), analgesics (8.16%), dietary supplements/herbals/homeopathic (7.00%), and foreign bodies/toys/miscellaneous (6.51%). Drug identification requests comprised 3.64% of all information contacts. NPDS documented 4,497 human exposures resulting in death; 3,809 (84.7%) of these were judged as related (RCF of 1-Undoubtedly responsible, 2-Probably responsible, or 3-Contributory). CONCLUSIONS: These data support the continued value of PC expertise and the need for specialized medical toxicology information to manage more serious exposures. Unintentional and intentional exposures continue to be a significant cause of morbidity and mortality in the US. The near real-time status of NPDS represents a national public health resource to collect and monitor US exposure cases and information contacts. The continuing mission of NPDS is to provide a nationwide infrastructure for surveillance for all types of exposures (e.g., foreign body, infectious, venomous, chemical agent, or commercial product), and the identification and tracking of significant public health events. NPDS is a model system for the near real-time surveillance of national and global public health.

Niacin toxicity resulting from urine drug test evasion.

BACKGROUND: Niacin, a well-established agent for treating dyslipidemia, has been promoted on the Internet as a method for passing urine drug screening, although there are no data to support its use for this purpose. In a handful of cases, this practice has resulted in serious niacin toxicity. OBJECTIVES: The aim of this article is to describe a unique clinical presentation of niacin toxicity. CASE REPORT: A 23-year-old previously healthy man presented to an Emergency Department with altered mental status, fever, acute renal failure, microangiopathic hemolytic anemia, thrombocytopenia, and coagulopathy. It was revealed that he had taken approximately 22.5 g of sustained-release niacin over the preceding 48 h in an attempt to pass a pre-employment urine drug screen. After a complicated hospital course that included mechanical ventilation for respiratory failure and hemodialysis for acute renal failure, the patient made a full recovery and was discharged 10 days after his initial presentation. CONCLUSION: After a massive niacin overdose, the young man in this case presented with a complex clinical picture that mimicked concurrent thrombotic thrombocytopenic purpura and disseminated intravascular coagulation. Although this patient was fortunate to make a full recovery, the case highlights the potential for multi-system toxicity with niacin overdose, and the potential for harm posed by medical misinformation on the Internet.

Calcium Carbonate for Elemental Lead Ingestions: Effect of Alkalinization on Elemental Lead Solubility in a Simulated Gastric Environment.

INTRODUCTION: Acute ingestion of elemental lead foreign bodies has resulted in multiple pediatric deaths. Elemental lead is relatively insoluble at alkaline pH. Furthermore, calcium decreases lead absorption by interfering with the lead absorptive receptor. We hypothesize that alkalinization of gastric fluid with an oral calcium-containing agent, such as calcium carbonate, will decrease lead solubility, thus reducing the potential for systemic lead absorption and toxicity. METHODS: This was an in vitro controlled study. One lead sphere (00 buckshot, cast 30 days prior) was randomly placed in each of ten tubes containing 20 mL simulated gastric fluid, with five tubes having 500 mg calcium carbonate added at 20 min and 140 min. We measured the fluid pH and the lead concentrations hourly for 4 h. We compared the median amount of total lead liberated after 4 h between the two groups using the Mann-Whitney U test. RESULTS: The pH of the gastric fluid only tubes remained 1 at every measurement, and the pH of the gastric fluid + calcium carbonate tubes was 6 at every measurement. At hour 4, the total amount of lead liberated in the soluble fraction in the control group vs the calcium carbonate group was 850 vs 12.4 mcg (95% CI for absolute difference: 605-964 mcg; p = 0.0079). CONCLUSIONS: Calcium carbonate antacid alkalinizes gastric fluid pH and dramatically decreases the total amount of solubilized lead by 60-fold. This project lends foundational evidence to a low-cost, widely available, pre-hospital strategy to decrease lead absorption after acute elemental lead ingestions.

2020 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 38th Annual Report.

INTRODUCTION: This is the 38th Annual Report of the American Association of Poison Control Centers' (AAPCC) National Poison Data System (NPDS). As of 1 January, 2020, all 55 of the nation's poison centers (PCs) uploaded case data automatically to NPDS. The upload interval was 6.15 [4.60, 8.62] (median [25%, 75%]) minutes, effectuating a near real-time national exposure and information database and surveillance system. METHODS: We analyzed the case data tabulating specific indices from NPDS. The methodology was similar to that of previous years. Where changes were introduced, the differences are identified. Cases with medical outcomes of death were evaluated by a team of medical and clinical toxicologist reviewers using an ordinal scale of 1-6 to assess the Relative Contribution to Fatality (RCF) of the exposure. RESULTS: In 2020, 3,316,738 closed encounters were logged by NPDS: 2,128,198 human exposures, 66,745 animal exposures, 1,116,568 information requests, and 5,160 human confirmed nonexposures. Total encounters showed a 28.9% increase from 2019, while health care facility (HCF) human exposure cases decreased by 10.6%. While all information requests increased by 218.0%, medication identification (Drug ID) requests decreased by 31.5%, and human exposure cases decreased by 0.928%. Medical Information requests showed a 32.6-fold increase, reflecting COVID-19 pandemic calls to PCs. Human exposures with less serious outcomes have decreased 1.90% per year since 2008, while those with more serious outcomes (moderate, major or death) have increased 4.59% per year since 2000.Consistent with the previous year, the top 5 substance classes most frequently involved in all human exposures were analgesics (10.3%), household cleaning substances (8.37%), cosmetics/personal care products (6.53%), antidepressants (5.30%), and sedatives/hypnotics/antipsychotics (4.92%). As a class, antidepressant exposures increased most rapidly, by 1,793 cases/year (5.84%/year) over the past 10 years for cases with more serious outcomes.The top 5 most common exposures in children age 5 years or less were cosmetics/personal care products (11.8%), household cleaning substances (11.3%), analgesics (7.57%), foreign bodies/toys/miscellaneous (6.71%), and dietary supplements/herbals/homeopathic (6.44%). Drug identification requests comprised 2.89% of all information contacts. NPDS documented 4,488 human exposures resulting in death; 3,869 (86.2%) of these were judged as related (RCF of 1-Undoubtedly responsible, 2-Probably responsible, or 3-Contributory). CONCLUSIONS: These data support the continued value of PC expertise and need for specialized medical toxicology information to manage more serious exposures. Unintentional and intentional exposures continue to be a significant cause of morbidity and mortality in the US. The near real-time status of NPDS represents a national public health resource to collect and monitor US exposure cases and information contacts. The continuing mission of NPDS is to provide a nationwide infrastructure for surveillance for all types of exposures (e.g., foreign body, infectious, venomous, chemical agent, or commercial product), and the identification and tracking of significant public health events. NPDS is a model system for the near real-time surveillance of national and global public health.

Time requirements for management of exposure and information cases by one regional poison center.

Background: Poison control centers (PCCs) manage millions of information and exposure cases a year. Exposure cases are almost always managed on-site (i.e., at "home") or at a health care facility (HCF). Over the last 10 years, there have been significant changes in the composition of cases managed by PCCs with an overall decrease in total cases but an increase in exposures managed at an HCF. The management and documentation of HCF cases may require more time than cases managed on-site or information cases. Time-work data are needed to accurately gauge the staff resources needed to address these changes.Methods: One poison center with an annual case volume of 74,000 conducted a time-work study of total case management time for a subset of cases: exposures Managed on-site and Managed at an HCF as well as information Drug identification cases. Specialists tracked the time spent communicating, managing, researching, consulting, and documenting. Additionally, the PCC medical records and phone call database were audited to ensure all calls and documented efforts related to a case were included.Results: Cases Managed at an HCF (n = 140) took more time (mean 45.8 min, median 29.3 min) than those Managed on-site (n = 430; mean 7.4 min, median 5.9 min) or Drug identification case (n = 392; mean 2.7 min, median 2.2 min); this difference was significant (p<.0001). There were 32 cases (23%) Managed at an HCF that required more than 1 h for total management; no Managed On-site or Drug identification cases required more than 33 min.Conclusions: The time required for one PCC to manage cases at an HCF was approximately six times longer than cases that were managed on-site. With PCC case volume and composition changing, previous staffing assumptions may no longer hold true. It would be incorrect to base staffing requirements on case volume alone without scrutiny of case types.

2019 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 37th Annual Report.

Introduction: This is the 37th Annual Report of the American Association of Poison Control Centers' (AAPCC) National Poison Data System (NPDS). As of 1 January, 2019, all 55 of the nation's poison centers (PCs) uploaded case data automatically to NPDS. The upload interval was 6.52 [6.12, 8.68] (median [25%, 75%]) minutes, creating a near real-time national exposure and information database and surveillance system.Methods: We analyzed the case data tabulating specific indices from NPDS. The methodology was similar to that of previous years. Where changes were introduced, the differences are identified. Cases with medical outcomes of death were evaluated by a team of medical and clinical toxicologist reviewers using an ordinal scale of 1-6 to assess the Relative Contribution to Fatality (RCF) of the exposure.Results: In 2019, 2,573,180 closed encounters were logged by NPDS: 2,148,141 human exposures, 68,711 animal exposures, 351,163 information requests, 5,078 human confirmed nonexposures. Total encounters showed a 1.70% increase from 2018, while health care facility (HCF) human exposure cases remained nearly steady with a slight decrease of 0.495%. All information requests decreased by 4.58%, medication identification (Drug ID) requests decreased by 29.7%, and human exposure cases increased by 2.30%. Human exposures with less serious outcomes have decreased 2.08% per year since 2008, while those with more serious outcomes (moderate, major or death) have increased 4.61% per year since 2000.Consistent with the previous year, the top 5 substance classes most frequently involved in all human exposures were analgesics (11.0%), household cleaning substances (7.13%), cosmetics/personal care products (6.16%), antidepressants (5.32%), and sedatives/hypnotics/antipsychotics (5.21%). As a class, antidepressant exposures increased most rapidly, by 1,957 cases/year (3.90%/year) over the past 10 years for cases with more serious outcomes.The top 5 most common exposures in children age 5 years or less were cosmetics/personal care products (11.4%), household cleaning substances (10.5%), analgesics (8.97%), foreign bodies/toys/miscellaneous (7.17%), and dietary supplements/herbals/homeopathic (5.06%). Drug identification requests comprised 13.4% of all information contacts. NPDS documented 2,619 human exposures resulting in death; 2,048 (78.2%) of these were judged as related (RCF of 1-Undoubtedly responsible, 2-Probably responsible, or 3-Contributory).Conclusions: These data support the continued value of PC expertise and need for specialized medical toxicology information to manage more serious exposures. Unintentional and intentional exposures continue to be a significant cause of morbidity and mortality in the US. The near real-time status of NPDS represents a national public health resource to collect and monitor US exposure cases and information contacts. The continuing mission of NPDS is to provide a nationwide infrastructure for surveillance for all types of exposures (e.g., foreign body, infectious, venomous, chemical agent, or commercial product), and the identification and tracking of significant public health events. NPDS is a model system for the near real-time surveillance of national and global public health.

Urinary Gadolinium Levels After Contrast-Enhanced MRI in Individuals with Normal Renal Function: a Pilot Study.

INTRODUCTION: Gadolinium-based contrast agents (GBCA) have been used to enhance magnetic resonance imaging (MRI) since 1985. Recently, the media and online groups have voiced concerns about gadolinium deposition in patients with normal renal function based on "elevated" urinary gadolinium levels. The determination of increased urinary gadolinium levels is based on reference ranges developed in individuals with normal renal function who were never exposed to GBCA. Studies suggest an elevated gadolinium urinary elimination greater than 72 h post GBCA scan. We evaluated urine gadolinium concentrations over a 30-day period in patients administered GBCA. METHODS: In this prospective, observational pilot study, we enrolled subjects between 18 and 65 years of age with normal renal function who received GBCA for the first time. Urinary gadolinium was measured at days zero (prior to GBCA exposure), 3, 10, and 30 after GBCA exposure. We compared urinary gadolinium levels after GBCA exposure to the current reference range and calculated an estimated duration of "elevated" gadolinium urine levels in the average patient. RESULTS: All 13 subjects had 24-h urinary gadolinium levels higher than 0.7 µg/24 h with means of 1944 (± 1432) µg/24 h on day 3, 301 (± 218) µg/24 h on day 10, and 34 (± 33) µg/24 h on day 30. Based on calculated urinary gadolinium elimination kinetics, we estimate urinary gadolinium levels will often remain above the current reference range for > 50 days. CONCLUSION: The current reference range of 0.7 µg/24 h for 24 h urinary gadolinium is not applicable to patients for at least 30 days following GBCA exposure.

2018 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 36th Annual Report.

Introduction: This is the 36th Annual Report of the American Association of Poison Control Centers' (AAPCC) National Poison Data System (NPDS). As of 1 January, 2018, 55 of the nation's poison centers (PCs) uploaded case data automatically to NPDS. The upload interval was 7.72 [6.90, 12.0] (median [25%, 75%]) minutes, creating a near real-time national exposure and information database and surveillance system.Methods: We analyzed the case data tabulating specific indices from NPDS. The methodology was similar to that of previous years. Where changes were introduced, the differences are identified. Cases with medical outcomes of death were evaluated by a team of medical and clinical toxicologist reviewers using an ordinal scale of 1-6 to assess the Relative Contribution to Fatality (RCF) of the exposure.Results: In 2018, 2,530,238 closed encounters were logged by NPDS: 2,099,751 human exposures, 57,017 animal exposures, 368,025 information requests, 5,346 human confirmed nonexposures, and 99 animal confirmed nonexposures. United States PCs also made 2,621,242 follow-up calls in 2018. Total encounters showed a 2.96% decline from 2017, while health care facility (HCF) human exposure cases remained nearly steady with a slight decrease of 0.261%. All information requests decreased by 15.5%, medication identification (Drug ID) requests decreased by 30.2%, and human exposure cases decreased by 0.729%. Human exposures with less serious outcomes have decreased 2.33% per year since 2008, while those with more serious outcomes (moderate, major or death) have increased 4.45% per year since 2000.Consistent with the previous year, the top 5 substance classes most frequently involved in all human exposures were analgesics (10.8%), household cleaning substances (7.28%), cosmetics/personal care products (6.53%), sedatives/hypnotics/antipsychotics (5.53%), and antidepressants (5.22%). For cases with more serious outcomes, sedative/hypnotics/antipsychotics exposures were the class that increased most rapidly, by 1,828 cases/year (9.21%/year) over the past 18 years. Over just the past 10 years (for cases with the most serious outcomes) antidepressant exposures increased most rapidly, by 1,887 cases/year (7.02%/year).The top 5 most common exposures in children age 5 years or less were cosmetics/personal care products (12.1%), household cleaning substances (10.7%), analgesics (9.04%), foreign bodies/toys/miscellaneous (6.87%), and topical preparations (4.69%). Drug identification requests comprised 18.2% of all information requests. NPDS documented 3,111 human exposures resulting in death; 2,582 (83.0%) of these were judged as related (RCF of 1-Undoubtedly responsible, 2-Probably responsible, or 3-Contributory).Conclusions: These data support the continued value of PC expertise and need for specialized medical toxicology information to manage more serious exposures. Unintentional and intentional exposures continue to be a significant cause of morbidity and mortality in the US. The near real-time status of NPDS represents a national public health resource to collect and monitor US exposure cases and information requests. The continuing mission of NPDS is to provide a nationwide infrastructure for surveillance for all types of exposures (e.g., foreign body, infectious, venomous, chemical agent, or commercial product), and the identification and tracking of significant public health events. NPDS is a model system for the near real-time surveillance of national and global public health.

Detection of ingested nitromethane and reliable creatinine assessment using multiple common analytical methods.

AIM: Nitromethane, found in fuels used for short distance racing, model cars, and model airplanes, produces a falsely elevated serum creatinine with standard creatinine analysis via the Jaffé method. Erroneous creatinine elevation often triggers extensive testing, leads to inaccurate diagnoses, and delayed or inappropriate medical interventions. Multiple reports in the literature identify "enzymatic assays" as an alternative method to detect the true value of creatinine, but this ambiguity does not help providers translate what type of enzymatic assay testing can be done in real time to determine if there is indeed false elevation. METHODS: We report seven cases of ingested nitromethane where creatinine was determined via Beckman Coulter® analyser using the Jaffé method, Vitros® analyser, or i-Stat® point-of-care testing. Nitromethane was detected and semi-quantified using a common clinical toxic alcohol analysis method, and quantified by headspace-gas chromatography-mass spectrometry. RESULTS: When creatinine was determined using i-Stat® point-of-care testing or a Vitros® analyser, levels were within the normal range. Comparatively, all initial creatinine levels obtained via the Jaffé method were elevated. Nitromethane concentrations ranged from 42 to 310 µg/mL. CONCLUSIONS: These cases demonstrate reliable assessment of creatinine through other enzymatic methods using a Vitros® analyser or i-STAT®. Additionally, nitromethane is detectable and quantifiable using routine alcohols gas chromatography analysis and by headspace-gas chromatography-mass spectrometry.

Evaluation of toxicity after acute accidental methotrexate ingestions in children under 6 years old: a 16-year multi-center review.

CONTEXT: There is little data on the frequency of adverse events following acute methotrexate ingestions in pediatric patients. Likewise, recommendations for observation length, site and management strategies in this population are not well established. Therefore, most recommendations are modeled after management of chronic overdose in patients with underlying medical conditions. OBJECTIVE: The primary objective of this study is to determine the frequency of acute toxicity after acute methotrexate accidental unsupervised ingestions in patients less than six years. In addition, we describe the frequency of late toxicity and characterize the management site and approaches. MATERIALS AND METHODS: This is a retrospective cohort study of pediatric accidental unsupervised methotrexate ingestions reported to six poison centers in the United States over a 16 year period. Demographic information, exposure details, signs, symptoms, treatments, length and location of observation and outcomes were collected. RESULTS: 103 patients met inclusion criteria. Methotrexate dose was reported in 86 patients (84%) and ranged from 1.3 mg-75 mg. The majority of cases (97%) ingested a dose ≤20 mg. The significant majority of cases experienced no clinical effects (99 of 103 cases; 96%). Three children experienced minor outcome (3%). There were no patients with a major outcome or death. CONCLUSIONS: The incidence of toxicity from pediatric single, acute ingestions of methotrexate is rare and when it occurs is generally limited to no or only minimally concerning effects. Because concentrations from single ingestions were consistent with low subtoxic exposures, we believe that home monitoring without hospital referral and without methotrexate specific therapy is reasonable in those with acute ingestions up to 20 mg.