Extracorporeal Treatment in Phenytoin Poisoning: Systematic Review and Recommendations from the EXTRIP (Extracorporeal Treatments in Poisoning) Workgroup.

The Extracorporeal Treatments in Poisoning (EXTRIP) Workgroup conducted a systematic literature review using a standardized process to develop evidence-based recommendations on the use of extracorporeal treatment (ECTR) in patients with phenytoin poisoning. The authors reviewed all articles, extracted data, summarized findings, and proposed structured voting statements following a predetermined format. A 2-round modified Delphi method was used to reach a consensus on voting statements, and the RAND/UCLA Appropriateness Method was used to quantify disagreement. 51 articles met the inclusion criteria. Only case reports, case series, and pharmacokinetic studies were identified, yielding a very low quality of evidence. Clinical data from 31 patients and toxicokinetic grading from 46 patients were abstracted. The workgroup concluded that phenytoin is moderately dialyzable (level of evidence = C) despite its high protein binding and made the following recommendations. ECTR would be reasonable in select cases of severe phenytoin poisoning (neutral recommendation, 3D). ECTR is suggested if prolonged coma is present or expected (graded 2D) and it would be reasonable if prolonged incapacitating ataxia is present or expected (graded 3D). If ECTR is used, it should be discontinued when clinical improvement is apparent (graded 1D). The preferred ECTR modality in phenytoin poisoning is intermittent hemodialysis (graded 1D), but hemoperfusion is an acceptable alternative if hemodialysis is not available (graded 1D). In summary, phenytoin appears to be amenable to extracorporeal removal. However, because of the low incidence of irreversible tissue injury or death related to phenytoin poisoning and the relatively limited effect of ECTR on phenytoin removal, the workgroup proposed the use of ECTR only in very select patients with severe phenytoin poisoning.

An Observational Study of the Factor Xa Inhibitors Rivaroxaban and Apixaban as Reported to Eight Poison Centers.

STUDY OBJECTIVE: Rivaroxaban and apixaban are part of a new group of oral anticoagulants targeting factor Xa and approved by the Food and Drug Administration in 2011 and 2012. These oral anticoagulants are administered at fixed daily doses, without the need for laboratory-guided adjustments. There are limited data available on supratherapeutic doses or overdose of the oral Xa inhibitors. This study characterizes the clinical effect in patients exposed to rivaroxaban and apixaban. METHODS: A retrospective study collected data from 8 regional poison centers covering 9 states. Cases were initially identified by a search of the poison centers' databases for case mentions involving a human exposure to Xarelto, rivaroxaban, Eliquis, or apixaban. Inclusion criteria included single-substance exposure. Exclusion criteria were animal exposure, polysubstance exposure, or information call. Data for the study were collected by individual chart review, including case narratives, and compiled into a single data set. RESULTS: There were 223 patients: 124 (56%) were female patients, mean age was 60 years, and 20 were children younger than 12 years (9%). One hundred ninety-eight patients ingested rivaroxaban (89%) and 25 ingested apixaban (11%). Dose was reported in 182 rivaroxaban patients, with a mean dose of 64.5 mg (range 15 to 1,200 mg), and in 21 apixaban patients, with a mean dose of 9.6 mg (range 2.5 to 20 mg). For rivaroxaban, prothrombin time was measured in 49 patients (25%) and elevated in 7; partial thromboplastin time, measured in 49 (25%) and elevated in 5; and international normalized ratio, measured in 61 (31%) and elevated in 13. For apixaban, prothrombin time was measured in 6 patients (24%) and elevated in none; partial thromboplastin time, measure in 6 (24%) and elevated in none; and international normalized ratio, measured in 5 patients (20%) and elevated in none. Bleeding was reported in 15 patients (7%): 11 rivaroxaban and 4 apixaban. The site of bleeding was gastrointestinal (8), oral (2), nose (1), bruising (1), urine (1), and subdural (1). The subdural bleeding occurred after fall and head injury. All cases with bleeding involved long-term ingestions. Coagulation test results were normal in most patients with bleeding: prothrombin time 5 of 6 (83%), partial thromboplastin time 5 of 6 (83%), and international normalized ratio 5 of 9 (55%). Blood products were used in 7 rivaroxaban patients (1 suicide) and 3 apixaban patients. No bleeding or altered coagulation test results occurred in children, which all involved a one-time ingestion. All 12 suicide attempts involved rivaroxaban: altered coagulation test results occurred for 5 patients (42%), no bleeding occurred in any suicide attempt patient, 1 patient was treated with fresh frozen plasma (international normalized ratio 12.47), and dose by patient history did not predict risk of altered coagulation or bleeding. Two rivaroxaban patients experienced elevation of hepatic transaminase levels greater than 1,000 U/L. CONCLUSION: Bleeding after Xa inhibitor ingestion as a single agent is uncommon. Prothrombin time, partial thromboplastin time, or international normalized ratio may be elevated in a minority of cases but appears unreliable to measure risk of bleeding. Massive acute ingestion in suicide attempt may result in significant anticoagulation. Single exploratory ingestion by children was not associated with toxicity.

Why are we Still Dialyzing Overdoses to Tricyclic Antidepressants? A subanalysis of the NPDS database.

A recent analysis of the American Association of Poison Control Centers database, showed that poisonings from toxins not usually considered amenable to extracorporeal purification ("non-classic toxins" such as ethanol and tricyclic antidepressants) continue to be reported. This publication investigates factors that may explain these findings. Our results suggest that: 1) the relatively high absolute number of ECTR performed for non-classic toxins may simply reflect the large number of exposures to these toxins, 2) poisoning from another toxin may have been the reason for ECTR initiation in some exposures to non-classic toxins, 3) poisoning from non-classic toxins may receive ECTR for purposes other than toxin removal, and 4) the decisional threshold to initiate ECTR may be lower for non-classic toxins because of heightened toxicity.

Practice Trends in the Use of Extracorporeal Treatments for Poisoning in Four Countries.

Extracorporeal treatments (ECTRs) such as hemodialysis (HD), enhance the elimination of a small number of toxins. Changes in overdose trends, prescribing practices, antidotes, and dialysis techniques may alter the indications and rates of ECTR use over time. This study analyzed trends in ECTR for poisonings in four countries. A retrospective study of national poison center databases from the United States, Denmark, United Kingdom, and five regional databases within Canada was performed. All cases of patients receiving an ECTR were included. ECTR cases were totalled annually and reported as annual rates per 100,000 exposures with stratification per types of ECTR and toxins. The data collection varied by countries. United States, 1985-2014; United Kingdom, 2011-2013; Denmark, 2005-2014, and regions of Canada as follows: Alberta, 1991-2015; Saskatchewan, 2001-2015; Nova Scotia-PEI, 2006-2015; Quebec, 2008-2014; Ontario-Manitoba, 2009-2015; British Columbia, 2012-2015. During the study period, the total number of ECTRs and rates per 100,000 exposures, respectively, were: United States, 40,258 and 65.7; United Kingdom, 343 and 232.6; Denmark, 616 and 305.5; Canada, 2709 and 177.5; case rates increased over time for the United States, Denmark, and Canada, but decreased in the United Kingdom. Across the United States and Denmark, HD was the preferred modality used. Toxins for which ECTR was most often used were: United States, ethylene glycol; Canada, methanol; United Kingdom, ethylene glycol; Denmark, salicylates. A high number of ECTRs were performed for atypical toxins such as acetaminophen and benzodiazepines. These data demonstrate a growing use of HD for poisoning with significant regional variations in the overall rates and indications.

Trends in toxic alcohol exposures in the United States from 2000 to 2013: a focus on the use of antidotes and extracorporeal treatments.

Morbidity and mortality from toxic alcohols like ethylene glycol and methanol remain prevalent worldwide. The introduction of fomepizole, a potent blocker of alcohol dehydrogenase, has modified current practice over the last 15 years. The aim of the study was to describe the characteristics of toxic alcohol poisoning reported to US poison centers, the trends in the incidence of antidote use and hemodialysis treatment, as well as the related mortality. A retrospective study of all electronic entries from the AAPCC National Poison Data System database, from the years 2000 to 2013 was reviewed. When considering all exposures, the great majority of patients had a benign outcome. Major effects (e.g., life threatening) occurred in 2.1% and 4.9% of methanol and ethylene glycol cases, respectively. Mortality rates were similar for both toxic alcohols, approximately 0.6%. When only considering ingestions reported to healthcare facilities, a major effect was reported in 9.5% and 20.5%, and the mortality rate was 2.9% and 2.4% for methanol and ethylene glycol exposures, respectively, and remained constant over time. The use of fomepizole increased statistically over the study period while that of ethanol decreased, until it became proportionally negligible by 2012-2013. The use of hemodialysis significantly decreased in "Early" ethylene glycol exposures during the study period. Similar to other reports, it appears that the use of fomepizole has largely supplanted ethanol as the antidote of choice in toxic alcohol exposures and may decrease the requirements for hemodialysis in patients poisoned with ethylene glycol who have no acidosis and normal kidney function.

Guidelines for reporting case studies on extracorporeal treatments in poisonings: methodology.

A literature review performed by the EXtracorporeal TReatments In Poisoning (EXTRIP) workgroup highlighted deficiencies in the existing literature, especially the reporting of case studies. Although general reporting guidelines exist for case studies, there are none in the specific field of extracorporeal treatments in toxicology. Our goal was to construct and propose a checklist that systematically outlines the minimum essential items to be reported in a case study of poisoned patients undergoing extracorporeal treatments. Through a modified two-round Delphi technique, panelists (mostly chosen from the EXTRIP workgroup) were asked to vote on the pertinence of a set of items to identify those considered minimally essential for reporting complete and accurate case reports. Furthermore, independent raters validated the clarity of each selected items between each round of voting. All case reports containing data on extracorporeal treatments in poisoning published in Medline in 2011 were reviewed during the external validation rounds. Twenty-one panelists (20 from the EXTRIP workgroup and an invited expert on pharmacology reporting guidelines) participated in the modified Delphi technique. This group included journal editors and experts in nephrology, clinical toxicology, critical care medicine, emergency medicine, and clinical pharmacology. Three independent raters participated in the validation rounds. Panelists voted on a total of 144 items in the first round and 137 items in the second round, with response rates of 96.3% and 98.3%, respectively. Twenty case reports were evaluated at each validation round and the independent raters' response rate was 99.6% and 98.8% per validation round. The final checklist consists of 114 items considered essential for case study reporting. This methodology of alternate voting and external validation rounds was useful in developing the first reporting guideline for case studies in the field of extracorporeal treatments in poisoning. We believe that this guideline will improve the completeness and transparency of published case reports and that the systematic aggregation of information from case reports may provide early signals of effectiveness and/or harm, thereby improving healthcare decision-making.

A 9-state analysis of designer stimulant, "bath salt," hospital visits reported to poison control centers.

STUDY OBJECTIVE: A new generation of designer stimulants marketed as "bath salts" emerged in late 2010. The goal is to describe the epidemiologic emergence of designer stimulants in 9 states in the Midwest. METHODS: A retrospective review of the National Poison Data System was performed between November 1, 2010, and November 30, 2011. Inclusion criteria were health care-evaluated bath salts or other synthetic stimulants exposures. Cases were excluded if the exposure was unrelated to a designer stimulant. Demographic and clinical characteristics of cases were calculated and differences in outcome and exposure by generation were examined. RESULTS: One thousand six hundred thirty-three patients met the inclusion criteria. Age ranged from 1 day to 61 years (mean=29.2 years), with 67.9% male patients. The most common clinical features were agitation (62.2%), tachycardia (55.2%), and hallucinations (32.7%). In addition to 15.5% of patients having a major medical effect, 0.6% died. Reason for use was primarily intentional abuse (88.5%). However, 0.7% of patients reported withdrawal. Treatment involved primarily benzodiazepines (58.5%), with 8.7% of patients being intubated. Baby Boomers were more likely to have a major medical outcome (24.2%) and to report injection as the method of administration (8.6%-12.9%). CONCLUSION: Synthetic stimulants rapidly swept across the Midwest, resulting in more than 1,600 patients seeking medical care. Serious medical effects or death was observed in 16.1% of cases. Older generations were more likely to inject and to have a major medical outcome.

Forty years of National Poison Data System Annual Reports.

INTRODUCTION: The 40th National Poison Data System Annual Report from America's Poison Centers is published in this issue of Clinical Toxicology. This Commentary will focus on changes that have occurred over the years and emerging trends while highlighting some of the strengths and weaknesses of the system. FORTY YEARS OF NATIONAL POISON DATA SYSTEM ANNUAL REPORTS: The National Poison Data System now receives poison exposure data from all 50 states and territories of the United States, representing all levels of care and medical outcomes, and is collected in near real-time. The 2022 report is double in size from the 1983 report and shows changes in the distribution of exposure substances and at least a doubling in the percentage of calls from a health care facility, intentional exposures, and fatalities. There was also a more modest increase in cases managed in a health care facility, and a 40% drop in the percentage of cases managed in those under age 6. While total reported poison center cases have been decreasing since 2008, cases with more serious medical outcomes have steadily increased. To address the decline in the total number of less serious cases, an online tool was initiated for consumers to obtain simple individualized poisoning recommendations as an alternative to directly contacting a poison center. FENTANYL EXPOSURES AND TISSUE CONCENTRATIONS: Fentanyl exposures reported to the National Poison Data System have increased rapidly since 2019, driven by non-prescription fentanyl. Reporting of this was facilitated by the granularity of the generic coding schema and the ability to develop new generic codes rapidly, unlike some other national data sets. Total fentanyl exposures and those with more serious outcomes show a good correlation with national data on fentanyl deaths, demonstrating the ability of the National Poison Data System to function as a surveillance tool. Fentanyl concentrations reported to the National Poison Data System Fatality module showed antemortem concentrations to be slightly lower than postmortem concentrations, little difference between postmortem peripheral and central concentrations, and single substance concentrations slightly higher than cases with multiple substances. STRENGTHS AND WEAKNESSES: Strengths include the breadth of the database, granularity, contemporaneous data collection, near-real-time data submission allowing for automated toxicosurveillance activities, ability to rapidly activate emergency product codes for emerging situations, a robust web-based query tool, mapping of generic codes and clinical effects to other data dictionaries, and review by toxicologists of fatalities to assign a relative contribution. Weaknesses include voluntarily reported, non-verified exposures, interpreting reported medical outcomes (non-toxic and fatalities), lag-time in collecting data on new therapeutic modalities, and mortality data varying from that reported by other sources. CONCLUSION: Poison center data gives a robust, reproducible image of the populations that utilize poison center resources and seems to mirror trends noted from other data sources. This supports the continued need for poison centers in the information age to support the management of patients potentially exposed to poisons and those who are more severely poisoned.

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.

Benzodiazepine-associated atrioventricular block.

Dysrhythmias, although common in overdose situations, are not often seen after benzodiazepine exposures. We report two cases of transient atrioventricular block after benzodiazepine misuse. Case 1 is a 4-year-old boy who was found unresponsive after an ingestion of clonazepam. An electrocardiogram (EKG) performed on emergency department presentation demonstrated first-degree atrioventricular block (PR 206 ms). After flumazenil administration, he developed second-degree atrioventricular block (Mobitz Type 1). EKG abnormalities resolved by morning. Serum clonazepam was 478 ng/mL (laboratory clonazepam reference range, 10-75 ng/mL with a dose of up to 6 mg/day) 5 hours after being found unresponsive. Case 2 is a 23-year-old man who presented to the emergency department after ingesting risperidone, combination hydrocodone/acetaminophen, and alprazolam. On arrival, his EKG demonstrated sinus bradycardia with a PR interval of 182 msec. He subsequently developed second-degree atrioventricular block (Mobitz Type I). Sinus bradycardia with resolution of his atrioventricular block (PR 200 ms) was seen on a third EKG performed 5 hours after presentation. These two patients demonstrated transient first- and second-degree atrioventricular block after benzodiazepine exposure. Benzodiazepines have been shown to alter L-type Ca2+ channel function. This alteration in function may account for the dysrhythmias seen in our patients. Together, these cases serve to remind clinicians of this rare but potentially serious complication associated with benzodiazepine exposure.

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.

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.

Extracorporeal treatments for isoniazid poisoning: Systematic review and recommendations from the EXTRIP workgroup.

Isoniazid toxicity from self-poisoning or dosing errors remains common in regions of the world where tuberculosis is prevalent. Although the treatment of isoniazid poisoning is centered on supportive care and pyridoxine administration, extracorporeal treatments (ECTRs), such as hemodialysis, have been advocated to enhance elimination of isoniazid. No systematic reviews or evidence-based recommendations currently exist on the benefit of ECTRs for isoniazid poisoning. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup systematically collected and rated the available evidence on the effect of and indications for ECTRs in cases of isoniazid poisoning. We conducted a systematic review of the literature, screened studies, extracted data on study characteristics, outcomes, and measurement characteristics, summarized findings, and formulated recommendations following published EXTRIP methods. Forty-three studies (two animal studies, 34 patient reports or patient series, and seven pharmacokinetic studies) met inclusion criteria. Toxicokinetic or pharmacokinetic analysis was available for 60 patients, most treated with hemodialysis (n = 38). The workgroup assessed isoniazid as "Moderately Dialyzable" by hemodialysis for patients with normal kidney function (quality of evidence = C) and "Dialyzable" by hemodialysis for patients with impaired kidney function (quality of evidence = A). Clinical data for ECTR in isoniazid poisoning were available for 40 patients. Mortality of the cohort was 12.5%. Historical controls who received modern standard care including appropriately dosed pyridoxine generally had excellent outcomes. No benefit could be extrapolated from ECTR, although there was evidence of added costs and harms related to the double lumen catheter insertion, the extracorporeal procedure itself, and the extracorporeal removal of pyridoxine. The EXTRIP workgroup suggests against performing ECTR in addition to standard care (weak recommendation, very low quality of evidence) in patients with isoniazid poisoning. If standard dose pyridoxine cannot be administered, we suggest performing ECTR only in patients with seizures refractory to GABAA receptor agonists (weak recommendation, very low quality of evidence).

The MALAdy of metformin poisoning: Is CVVH the cure?

Inadvertent or intentional metformin overdose can result in death from refractory lactic acidosis. We report a death from metformin-induced refractory lactic acidosis despite aggressive care. A 49-year-old hypertensive diabetic female presented 1 hour after ingesting 60 tablets of 500 mg metformin and 20 combination tablets of 12.5 mg hydrochlorothiazide/20 mg lisinopril. She was awake and alert, with a blood glucose of 579 mg/dL. Chemistry panel revealed lactic acidosis and acute renal failure (arterial blood gas pH, 7.18; pCO(2), 15 mm Hg; pO(2), 127 mm Hg; HCO(3), 6 mmol/L; lactate, 9.6 mmol/L; and creatinine, 1.2 mg/dL [0.8 mg/dL previously]). She received normal saline, sodium bicarbonate, and insulin. On arrival to the intensive care unit she was obtunded, with a blood pressure of 40/25 mm Hg and had worsening acidosis and poor oxygenation (arterial blood gas pH, 6.79; pCO(2), 55; pO(2), 57; HCO(3), 8.4; and base excess of -25 on 100% fractional inspired oxygen). She was intubated and received additional fluid boluses, bicarbonate, and norepinephrine. Continuous veno-venous hemofiltration (CVVH) was started 6 hours after her ingestion. Metformin was 380 microg/mL on CVVH initiation. The patient developed pulseless electrical activity 30 hours after her ingestion, which recurred 20 minutes later. The family requested no further resuscitation. She died 31.5 hours after her ingestion. Metformin concentrations decreased to 97 microg/mL 28 hours after the ingestion on CVVH, with a first-order elimination half-life of 11.3 hours (r(2) = 0.99) and a clearance of 56.2 mL/min. Further investigations on the place of CVVH in the management of the poisoned patient with MALA unable to hemodynamically tolerate conventional hemodialysis may be needed.

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.

Temporal and geospatial trends of adolescent intentional overdoses with suspected suicidal intent reported to a state poison control center.

Background: In the United States, adolescent suicide attempts are increasing. Indiana has the highest rate of adolescent suicidal ideation in the US. Using the National Poison Data System (NPDS), we analyzed Indiana's increase in suicide attempts by poisoning. Methods: Utilizing NPDS and Toxicall data repositories, we selected 10-19 year-old intentional overdose cases with suspected suicidal intent from 2006-2016. Age, sex, outcome, involved substances and case volume by weekday and month were assessed. Geospatial analysis of the proportion of cases by county was also performed. To determine the association between known social determinants of health and adolescent intentional overdose cases with suspected suicidal intent, we correlated county-wide statistics from the County Health Rankings and Roadmaps dataset from 2010-2016 with the proportion of teen suicide cases by county. Results: Over the eleven years, adolescent intentional overdoses with suspected suicidal intent cases significantly increased starting in 2012 (p-value < .001). The majority of cases (73.7%) involved females with an average age of 15.96 ± 0.27 years. Monday and Tuesday had the highest rates and Saturday had the lowest. June and July had the lowest case rate while November had the highest. The most commonly involved agents were over-the-counter analgesics and antidepressants. Geospatial analysis shows an increased number of cases in the northern third of the State. Among county statistics analyzed, only violent crime was associated, albeit intermittently, with the 11-year proportion of adolescent intentional overdoses with suspected suicidal intent by county. Conclusions: Intentional overdoses with suspected suicidal intent involving adolescent females are significantly increasing. These rates correlate with the school schedule with summer months and weekends having a lower frequency of calls. We did not find associations between county wide social determinants of care with the exception of violent crime. Further studies are needed to establish the factors that might better predict adolescents at risk for suicide.

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.

Extracorporeal treatments in poisonings from four non-traditionally dialysed toxins (acetaminophen, digoxin, opioids and tricyclic antidepressants): A combined single-centre and national study.

The use of extracorporeal treatments (ECTRs) for poisonings with four non-traditionally dialysed toxins (NTDTs) is increasing in the United States. This study evaluated whether ECTRs are prescribed for toxin removal or the treatment of other medical illnesses or complications. We performed a 2-Phase retrospective analysis evaluating the main indication for ECTRs in patients with poisoning from a NTDT (defined for this study as acetaminophen, opioids, tricyclic antidepressants (TCAs) or digoxin) and ECTR. The first phase assessed all cases from a single site (New York City Poison Control Center) between the years 2000 and 2016, and the second phase surveyed all United States Poison Control Centers (PCCs). In Phase 1, demographics, toxin ingested and main indication for ECTR were extracted. In Phase 2, a query to the National Poison Data System using the a pragmatic subset of inclusion criteria from Phase 1 restricted to single toxin ingestions over a narrower time frame (2014-2016) provided the cases for study. A structured online questionnaire was sent to all United States PCCs to request their database review regarding the indication for ECTR for their cases. In Phase 1, 92 cases met inclusion criteria. In Phase 2, 519 cases were screened and 425 met inclusion criteria. In Phase 1 91/92 (98.9%) and Phase 2 411/425 (96.7%), of extracorporeal treatments were used to treat underlying medical conditions or poisoning-related complications rather than accelerate toxin removal. The increasing number of ECTRs reported in patients who ingested one of the four NTDTs thus appears to be for medical indications rather than attempts at toxin removal, a distinction that is important.

2017 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 35th Annual Report.

INTRODUCTION: This is the 35th Annual Report of the American Association of Poison Control Centers' (AAPCC) National Poison Data System (NPDS). As of 1 January 2017, 55 of the nation's poison centers (PCs) uploaded case data automatically to NPDS. The upload interval was 8.07 [7.32, 12.65] (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 2017, 2,607,413 closed encounters were logged by NPDS: 2,115,186 human exposures, 51,164 animal exposures, 435,540 information contacts, 5,424 human confirmed nonexposures, and 99 animal confirmed nonexposures. US PCs also made 2,680,625 follow-up calls in 2017. Total encounters showed a 3.79% decline from 2016, while health care facility (HCF) human exposure cases increased by 3.06%. All information contacts decreased by 11.5%, medication identification (Drug ID) requests decreased by 30.2%, and human exposure cases decreased by 2.03%. Human exposures with less serious outcomes have decreased 2.48% per year since 2008, while those with more serious outcomes (moderate, major or death) have increased 4.44% per year since 2000. Consistent with the previous year, the top 5 substance classes most frequently involved in all human exposures were analgesics (11.08%), household cleaning substances (7.43%), cosmetics/personal care products (6.76%), sedatives/hypnotics/antipsychotics (5.74%), and antidepressants (5.02%). As a class, sedative/hypnotics/antipsychotics exposures increased most rapidly, by 1962 cases/year (4.91%/year), over the last 17 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 (12.59%), household cleaning substances (10.96%), analgesics (9.18%), foreign bodies/toys/miscellaneous (6.39%), and topical preparations (4.84%). Drug identification requests comprised 22.1% of all information contacts. NPDS documented 3,208 human exposures resulting in death; 2,682 (83.6%) 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 need for specialized medical toxicology information to manage more serious exposures, despite a decrease in cases involving less 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.

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.