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Background: The diagnosis of toxic alcohol poisoning is often based on clinical presentation and nonspecific surrogate laboratory studies due to limited testing availability. Fomepizole is the recommended antidote and often administered empirically. The objective of this study is to identify substances that mimic toxic alcohols and compare key clinical factors between toxic alcohol and non-toxic alcohol exposures when fomepizole was administered., Methods: This study was a retrospective evaluation using the National Poison Data System from January 1, 2010 through December 31, 2021. Exposures were included if fomepizole was administered. Toxic alcohol exposures had ethylene glycol or methanol as a coded substance. For exposures not coded as a toxic alcohol, the first substance was described. Paracetamol (acetaminophen) exposures from 2020 and 2021 were excluded., Results: Fomepizole was reportedly used 25,110 times over 12 years. Use increased from 1,955 in 2010 to 2,710 in 2021. Most administrations were for reported toxic alcohol poisoning (60 percent) but use in reported non-toxic alcohol poisoning was greater starting in 2020. Toxic alcohol exposures were older (43.3 versus 39.8 years; P  < 0.001) and more likely male (65.7 percent versus 58.2 percent). Level of care was mostly a critical care unit (67.7 percent), which was less common in toxic alcohol (63.3 percent) than non-toxic alcohol exposures (74.2 percent). The most common non-toxic alcohol substances were ethanol (24.9 percent) or an unknown drug (17.5 percent). Acidosis, increased creatinine concentration, anion gap, and osmolal gap, and kidney failure were coded in a lower proportion of toxic alcohol exposures than non-toxic alcohol exposures ( P  < 0.001)., Discussion: The inability to provide rapid clinical confirmation of toxic alcohol poisoning results in the empiric administration of fomepizole to many patients who will ultimately have other diagnoses. Although fomepizole is relative well tolerated we estimated that this practice costs between $1.5 to $2.5 million. The major limitations of this work include the biases associated with retrospective record review, and the inability to confirm the exposures which may have resulted in allocation error., Conclusion: Most fomepizole use was for a presumed toxic alcohol. This recently shifted to greater use in likely non-toxic alcohol poisoning. Key difference between the groups suggest fomepizole administration was likely due to the difficulty in diagnosis of toxic alcohol poisoning along with the efficacy and safety of fomepizole. Increased toxic alcohol laboratory testing availability could improve timely diagnosis, reserving fomepizole use for toxic alcohol poisoning.

Introduction: Increased prescribing of antipsychotics and availability of new antipsychotics has resulted in increased exposures in children. Current data on aripiprazole, brexpiprazole, and cariprazine are limited., Methods: This was a retrospective database study utilizing the National Poison Data System from 2015 through 2021. We included cases of single substance exposures to aripiprazole, brexpiprazole, cariprazine, or lumateperone in children ages 0 to 5 years old with follow-up to a known outcome. Key outcomes were medical outcomes, clinical effects, and level of care if treated in a healthcare facility., Results: There were 3,573 aripiprazole, 137 brexpiprazole, 249 cariprazine, and one lumateperone exposure over the period. Primary outcomes were evaluated in 2,655 cases (2,390 aripiprazole, 96 brexpiprazole, and 169 cariprazine). Fifty-one percent were male and 77% were between 0 and 2 years old. Moderate effect was coded in 16.6% of aripiprazole, 23% of brexpiprazole, and 12% of cariprazine exposures. Major effect was coded in 0.6% of aripiprazole, 1% of brexpiprazole, and 2.4% of cariprazine exposures. Duration of symptoms was mostly between 8 and 24 h for 34.6% of aripiprazole, 30% of brexpiprazole, and 32% of cariprazine exposures. Over 60% of the children seen in a health care facility were discharged from the emergency department. The lowest doses resulting in at least a moderate effect and admission to a health care facility was 0.46 mg/kg for aripiprazole, 2.1 mg/kg for brexpiprazole, and 1.9 mg/kg for cariprazine. Important clinical effects included central nervous system depression, tremors, tachycardia, agitation, and vomiting., Conclusion: Reported ingestions of aripiprazole, brexpiprazole, or cariprazine may result in neurologic symptoms like central nervous system depression or seizures in children. The prolonged duration of symptoms resulted in admission for at least a day for many cases. Further research should address optimal monitoring time and location for these exposures.

Introduction: Almost half of exposures reported to United States (US) poison centers are exploratory ingestions in children under the age of 5 years. Pediatric cannabis exposures reported to US poison centers have risen over the last twenty years, with greater increases in the last 5 years. In 2020, the Coronavirus disease 2019 (COVID-19) pandemic resulted in widespread stay-at-home orders and subsequent changes in work, education, and daycare. This study describes the changes in pediatric cannabis exposures during the first nine months of the COVID-19 pandemic relative to the three years before the pandemic., Methods: Cases were identified from the National Poison Data System. Inclusion criteria was unintentional cannabis exposure in children aged 6 months to 5 years between January 1, 2017 and December 31, 2020. Analysis was performed with segmented regression of interrupted time series analysis comparing January 2017-March 2020 (pre-COVID-19) to April 2020-December 2020 (COVID-19 period). Autocorrelation was assessed using Dubin-Watson test., Results: There were 7,679 unintentional pediatric exposures from January 1, 2017 through December 31, 2020. There was a significant increase of 3.1% per month during the pre-COVID-19 period ( p  < .0001). A statistically significant immediate increase in number of exposures per month occurred in April 2020 (58.4%; p  < .0001). The slope in the COVID-19 period was -0.01% ( p  = .99). No autocorrelation was detected., Discussion and Conclusions: Unintentional cannabis exposures in children aged 6 months to 5 years reported to United States poison centers increased significantly after the initial COVID-19 stay-at-home orders. This trend may be associated with COVID-19 quarantines, increased time children are spending at home, increased availability of cannabis products in homes, or other reasons. Future efforts should evaluate specific factors that resulted in the observed increases in pediatric exposures.

Background: Cannabis exposures in children have risen sharply in recent years, resulting in increased hospital visits and admission to pediatric intensive care units (PICUs). The intent of this study was to describe the proportion of pediatric patients admitted to the PICU after unintentional cannabis ingestion that received critical care interventions (CCIs) along with describing trends over time in hospitalization, admission to the PICU, and clinical effects and treatments outside of the PICU., Methods: This was a retrospective database study utilizing the National Poison Data System (NPDS) from 1/1/2000 to 12/31/2020. Children 6 months to 12 years of age with single substance cannabis exposures were included., Results: A total of 12,882 cases were included. There was an increase in the proportion of cases seen in a hospital over time from 43.8% in 2000 to 54.6% in 2020 (range 29.1-62.6%). In patients seen in a HCF, the proportion admitted to the PICU was 9.5% in 2000 and 14% in 2020 (range: 5.6-29.0%). The 875 (6.8%) children admitted to the PICU were analyzed for the primary outcome. CCIs were performed in 69/875 (7.9%) cases that were admitted to the PICU. The most common CCIs in the PICU were intubation and sedation, 4.9 and 3.7%, respectively., Conclusions: Unintentional pediatric cannabis exposures are associated with clinically significant effects, including respiratory depression, hypotension, and bradycardia, but fewer than 5% of exposures were treated with CCIs, like intubation or vasopressors, in patients admitted to the PICU. Further work should assess specific reasons for admission to the PICU.

Background: Previous literature suggests a laboratory interference of n-acetylcysteine (NAC) with prothrombin time (PT) and the international normalized ratio (INR). Early publications focused on this interaction in the setting of an acetaminophen overdose and evaluated the INR of patients receiving intravenous NAC. However, there is limited literature describing the concentration-effect relationship of NAC to INR measurement in the absence of acetaminophen-induced hepatotoxicity at therapeutic NAC concentrations. The purpose of the study is to quantify the degree of interference of NAC on INR values at therapeutic concentrations correlating to each infusion of the regimen (ex. bag 1: 550 mcg/mL, bag 2: 200 mcg/mL, bag 3: 35 mcg/mL, double bag 3: 70 mcg/mL) and at supratherapeutic concentrations in vitro ., Methods: Blood samples were obtained from study volunteers. Each blood sample was transferred into vials containing 0.3 mL buffered sodium citrate 3.2% and spiked with various concentrations of NAC for final concentrations of 0, 35, 70, 200, 550, 1000, 2000, and 4000 mcg/mL. The samples were centrifuged and tested to determine PT and INR on two separate machines: Siemens CS-2500 and Stago SN1114559. We would require a sample size of 6 to achieve a power of 80% and a level of significance of 1.7% (two-sided). Differences between INRs at varying concentrations were determined by Friedman's test. For multiple comparisons, post hoc analysis was performed using Wilcoxon signed-rank test with Bonferroni adjustment. Analyses were performed with SAS version 9.4 (SAS Institute, Cary, NC)., Results: Participants included 11 healthy subjects: 8 males, 3 females, median age 30 years (range 25 - 58). Median and interquartile ranges (IQR) INR for the baseline samples were 1.09 (IQR 1.05, 1.16) for Siemens and 1.03 (IQR 0.99, 1.11) for Stago analyzers. There was a significant difference in INR between the therapeutic concentrations (baseline, 35, 70,200, or 550 µg/mL) (Siemens p  = .0008, Stago p  < .0001). The 550 µg/mL concentration with the Siemens analyzer was the only one compared separately and found to be significantly greater than the baseline (1.07 vs 1.22, p  = .02). For the Stago analyzer the 200 µg/mL and 500 µg/mL were compared and found to be significantly different from baseline (1.00 vs 1.07 and 1.19, adjusted p  = .02 and p  = .03, respectively). The largest INR increase seen was in one subject from a baseline of 1.07-1.32 with the 550 µg/mL concentration. Increases in concentrations to supratherapeutic levels resulted in a statistically significant non-linear increase in INR for all concentrations (Siemens p  < .0001, Stago p  < .0001). All of these concentrations were found to be significantly different from baseline (all adjusted p  < .05)., Conclusion: Although it was found that at therapeutic concentrations the in vitro presence of NAC affects INR measurements on two different machines, the change is of little clinical relevance. Supratherapeutic concentrations of NAC affect INR significantly, but the clinical utility of those results is limited by the rarity of those concentrations being measured.

Background: Limited data describe poisoning exposures in pregnant women. Previous studies are limited to inpatient populations, those seen only by toxicologists, or single poison centers. This study aimed to describe poison exposures reported to U.S. poison control centers in pregnant patients compared to non-pregnant controls., Methods: This was a retrospective observational study of exposures reported to the American Association of Poison Control Centers National Poison Data System from 2000 through 2019. Pregnant patients were included from 15-44 years along with a random sampling of 5:1 age and year matched control group of non-pregnant exposures. Demographics, primary substance, and known medical outcomes were described. Chi square analysis was performed for comparisons., Results: From 2000 to 2019, a total of 131,619 pregnant cases and 658,095 non-pregnant controls were identified. The median age was 27 years (IQR: 22, 31) for the matched groups. For known trimester of pregnancy: 29.8, 37.0, and 28.2% were in the first, second, and third trimester, respectively. Most common exposures were analgesics and cleaning products. Intentional exposures were more common in non-pregnant compared to pregnant cases (41.2 vs 21.9%; OR 2.71, 95% CI 2.67-2.75), mostly self-harm attempts (31.5 vs. 15.8%). Notably, there was a large discrepancy in the proportion of environmental exposures, with fewer in non-pregnant controls compared with pregnant cases (3.8 vs. 12.1%; OR 0.29, 95% CI 0.28-0.29). More non-pregnant cases had multiple substance exposures compared with pregnant cases (22.2 vs. 10.9%; OR 2.34, 95% CI 2.29-2.38). There were more moderate effect outcomes in non-pregnant compared with pregnant cases (13.2 vs. 6.3%; OR 2.25, 95% CI 2.20-2.30)., Conclusions: Outcomes of poisoning exposures in pregnant patients reported to U.S. poison centers are less serious compared to non-pregnant controls, likely due to the lower rates of intentional abuse and self-harm exposures and greater number of minimally toxic environmental exposures.

Introduction: Perampanel is indicated for partial onset seizures in children and adults. The mechanism is unique among antiepileptic agents as it inhibits glutamate activity on AMPA receptors. Currently, there are few published case reports describing overdose., Methods: This is a retrospective observational study of all single substance perampanel ingestions from January 2014 to December 2019 reported to the national poison data system (NPDS). The primary outcome is to describe the clinical effects of perampanel exposures. Secondary outcomes include evaluation of management and investigation of a dose-effect relationship for the purpose of triaging acute unintentional exposures., Results: A total of 138 exposures were reported to NPDS since the release of the agent. Median age was 20 years (IQR 10-38) with 68 (49.3%) males. The reason for exposure was most commonly therapeutic error (80, 58.0%), followed by exploratory ingestion (24, 17.4%), and suicidal ingestion (14, 10.1%). A total of six (4.3%) patients developed major effects, 20 (14.5%) moderate, 32 (23.2%) minor effects and 22 (15.9%) no effect. An additional 54 (39.1%) cases were not followed. Almost half of cases were managed at home. Of those that were in a healthcare facility (HCF) ( n  = 72), most were treated/evaluated and released (31, 43.1%), followed by admission to a non-critical care unit (20, 27.8%), and critical care unit (13, 18.1%). Most frequently reported symptoms were drowsiness (27, 19.6%), agitation (20, 14.5%), ataxia (13, 9.4%), and confusion (12, 8.7%). The most common therapies provided in a HCF were intravenous fluids (22,30.6%), followed by benzodiazepines (14, 19.4%), then other types of sedation (9, 12.5%). There were too few cases to determine a dose cut off for triaging., Conclusions: While drowsiness, agitation, ataxia, and confusion were the most often reported symptoms, close to 19% developed moderate/major effects and almost 4% of patients received potentially life-saving interventions.

Objective: This is a descriptive study evaluating fatal iatrogenic and in-hospital medication errors reported to United States poison centers., Methods: A retrospective evaluation of the National Poison Data System from 2000-2017 of all therapeutic errors with a scenario coded as iatrogenic/healthcare professional or occurring in a healthcare facility. Death abstracts were reviewed for details of the exposure and therapeutic error scenarios were recoded or added to the case as appropriate. Cases, where death was considered not related to the exposure, were excluded. Additionally, we created one additional scenario (rate-related) and one additional route of administration (intrathecal) to better describe the cases., Results: A total of 172 cases were evaluated. The majority of the patients were female (52.3%) with a median age of 58.5 years (range: 2 days to 96 years). The most commonly reported medication error was "other incorrect dose" (22.7%) followed by other/unknown error (15.1%). The route of exposure was primarily parenteral (54.9%), followed by ingestion (30.2%), then intrathecal (7.0%). The most common medications were cardiac drugs, chemotherapeutics, opioids, anticoagulants, and sedative-hypnotic/antipsychotics., Conclusions: Iatrogenic and in-hospital medication errors have been studied extensively with goals to reduce their occurrence. Specific controls to prevent incorrect dosing routes, 10-fold overdoses, and incorrect intrathecal administration have been instituted. Despite interventions, all three of these therapeutic errors continued to occur in 2017, suggesting that more preventive controls should be instituted.

Background and Objectives: Pediatric ingestions of amphetamines used in the treatment of Attention Deficit Hyperactivity Disorder (ADHD) are on the rise. Little data provide an amphetamine dose at which to refer pediatric unintentional ingestions to a healthcare facility for monitoring. We studied the dose at which unintentional ingestions of amphetamines develop symptoms and receive benzodiazepines. Methods: We performed a retrospective study from a single poison center from 1/1/2005 through 11/30/2018. We included single substance ingestion of amphetamine salts to treat ADHD in amphetamine-naïve children age 0-12 years followed to a known outcome. Poison center documentation was reviewed for signs and symptoms related to amphetamine toxicity and use of benzodiazepines. Results: We screened 1,394 cases and 160 met inclusion criteria. The mean age of patients was 1.8 years and 55% were male. The median dose of symptomatic patients (1.38 mg/kg) was greater than those without symptoms (0.83 mg/kg). The median amphetamine dose of patients receiving benzodiazepines (1.58 mg/kg) was also greater than for patients not receiving benzodiazepines (1.0 mg/kg). A dose threshold of greater than 0.75 mg/kg was 100% sensitive and 36.8% specific for benzodiazepine administration and 93.9% sensitive and 47.4% specific for presence of any symptoms. Conclusions: The median dose of amphetamines ingested by patients receiving benzodiazepines was greater than those not receiving benzodiazepines. No child with a dose of ≤0.75 mg/kg received benzodiazepines. Prospective studies should be performed to assess triage guidelines and referral doses.

Objectives: To date, very little literature describes the outcomes of acute unintentional ingestions of lithium in young children. This study aimed to describe the clinical effects and outcomes reported in these patients reported to the National Poison Data System (NPDS). Methods: This is a retrospective observational study of acute unintentional lithium ingestions in children <6 years of age. The primary intent of the study was to characterize acute unintentional exposures to lithium in children in this age group. As a secondary outcome, we sought to identify a weight-based threshold to empirically refer patients into a healthcare facility for symptoms consistent with moderate effect or worse. The American Association of Poison Control Centers' NPDS was queried for all acute ingestions of lithium salts in children <6 years of age from 2000 to 2018. Inclusion criteria were single substance ingestions, unintentional-general exposure (i.e., exploratory ingestion), and followed to a known outcome or coded as potentially toxic exposure unable to follow and the patient was experiencing symptoms. Results: A total of 3045 single-substance exploratory ingestions of lithium were reported to poison centers that showed a decrease over time, consistent with decreasing use of lithium and decreasing calls to poison centers. Of the 3045 cases, we excluded 1178 leaving 1863 cases for analysis. Median age was 2 years (IQR: 1.5, 2) with 51% male cases. Management site was primarily non-health care facility ( n  = 808; 43.4%) with 569 (30.5%) already in a healthcare facility (HCF) when the Poison Control Center (PCC) was called and 477 (25.6%) referred to a HCF. The route of exposure was most commonly ingestion ( n  = 1853; 99.5%) and site of exposure was primarily home (1743; 93.6%). Medical outcomes were predominantly no effect and minor effect. There were 262 related clinical effects were reported in 184 patients (10%). The most frequently reported were vomiting ( n  = 76), drowsiness/lethargy ( n  = 58), other ( n  = 22), and ataxia ( n  = 20). Clinical effects lasted ≤2 h for 65 (33%), 2-8 h for 57 (28.9%), 8-24 h for 51 (25.9%), 1-3 days for 11 (5.6%), and >3 days to ≤1 week for 1 (0.5%); no cases resulted in clinical effects thought to be permanent and no deaths were reported. There were 1173 treatments provided to 857 patients. The most common treatments were basic and are readily performed at home; dilution ( n  = 492) and food/snack ( n  = 180). A smaller subset of patients received care that could likely only be provided in a healthcare facility including IV fluids ( n  = 173), other ( n  = 120), whole bowel irrigation ( n  = 46), single dose activated charcoal ( n  = 41), syrup of ipecac ( n  = 34), and lavage ( n  = 31). No patients received hemodialysis. A total of 425 of the exposures were referred to a healthcare facility by the PCC which had a dose coded. There was no difference in dose that resulted to referral to a healthcare facility over time ( p  = 0.2747). Due to the small number of moderate/major effect cases with dose information, we were unable to identify a dose-based threshold for referral to HCF. Conclusions: Severe outcomes after unintentional ingestion of lithium in pediatric patients are rare. It is likely that most asymptomatic pediatric patients <6 years do not need to be referred to the hospital after ingestion of lithium.

Background: Prepacked naloxone kits (PNKs) are frequently used to reverse opioid intoxication. It is unknown if the presence of illicitly manufactured fentanyl and its analogs (IMFs) in heroin supply is affecting the PNK doses given by laypersons. We investigated the trend of PNK dose administered to reverse opioid toxicity in suspected/undifferentiated opioid intoxication. Methods: We retrospectively reviewed PNK administrations reported to the Maryland Poison Center between 1 January 2015 and 15 October 2017. Primary outcome was the mean PNK dose administered to reverse opioid-induced central nervous system and ventilatory depression. Secondary outcomes included the reversal rate of opioid toxicity, patient disposition, and survival rate. Results: Our analysis involved 1139 PNK administrations. The mean age of subjects was 34.3 years; 68.8% ( n  = 781) were male. Ventilatory depression was present in 98.2% ( n  = 958) of cases, and 97% ( n  = 1097) were unresponsive. Law enforcement administered the majority of PNK (91.0%; n  = 1035); the primary route was intranasal (97.9%; n  = 1051). Toxicity was reversed in 79.2% ( n  = 886) of overdose victims after a mean PNK dose of 3.12 mg. EMS personnel gave 291 subjects additional naloxone (mean: 2.2 mg), reversing opioid toxicity in 94.2% ( n  = 254). Between 2015 and 2017, the mean PNK dose increased from 2.12 to 3.63 mg ( p  < .0001) while the reversal rate decreased from 82.1% to 76.4% ( p  = .04). One hundred and eighty-two patients (15.9%) refused transport; of those transported to a hospital, 73.4% ( n  = 569) were treated and released and 12.4% ( n  = 96) required hospitalization. Ninety-six percent ( n  = 1092) of the subjects survived. Forty subjects were pronounced dead at the scene. Fentanyl or its analog was detected in 36 of 55 opioid-related deaths (65.5%). Conclusions: PNK administration reversed toxicity in the majority of patients with undifferentiated opioid intoxication. Between 2015 and 2017, increasing doses of PNK were administered but the reversal rate decreased. These trends are likely multifactorial, including increasing availability of IMFs.

Background: Widespread use of the Internet has increased availability of numerous products. Multiple published cases highlight that toxic xenobiotics are available for purchase online. Most cases describe purchase from the deep web. We sought to identify extremely hazardous substances available from an online retailer. Methods: Over a 10-month period, the online retailer Amazon.com ® was searched for each of the products listed by the Environmental Protection Agency's "List of Extremely Hazardous Substances." Product names, availability on Amazon Prime ® , need for a business account, price, and quantity were collated. Results: We identified 79/340 (23.2%) of these substances were available on Amazon.com ® . Almost one-third of the available substances were eligible for Amazon Prime ® . Approximately one-third of the products were available in an amount that could be toxic by purchasing a single unit (31/79). Of these 31 products, only four required a business account, 18 were eligible for Amazon Prime ® , and nine were neither eligible for Prime nor required a business account. Notable products include sodium azide, acrylamide, mercuric acetate, and hydrazine. Conclusions: The ease of purchase and ready availability of such highly toxic substances is concerning. Online retailers like Amazon.com ® should consult with toxicologists or other qualified experts and governmental agencies to identify which products should be removed or restricted to business accounts.

Background : Therapeutic errors are costly and result in unplanned hospital visits. Recent poison center studies on therapeutic errors have focused on coded data from either the National Poison Data System (NPDS) or individual poison centers. Approximately 21% of therapeutic errors reported to NPDS are coded as "other incorrect dose" (OI) or "other/unknown therapeutic error" (OU). The purpose of this study was to characterize errors coded as OI or OU reported to a single poison center. Methods : Retrospective, single poison center chart review was conducted of therapeutic error exposures with at least one scenario coded as OI or OU seen in or referred to hospitals from 1/1/2000 to 9/30/2017. Cases were reviewed and re-coded to predefined or newly created scenarios. Results : A total of 3413 cases were identified. There were 726 cases assessed as not therapeutic errors and re-coded as either intentional misuse (430), adverse reaction drug (204), or other non-therapeutic errors (82). Of the remaining cases, 1726 cases were re-coded to one of the 16 existing therapeutic error scenarios. After re-coding, there remained 971 coded as OI or OU. Most were due to double, triple, quadruple, or higher than recommended dose (477/971); an additional common error was mistaken strength (81/971). The remaining scenarios occurred in fewer than 50 cases each with greater than 40 different scenarios such that additional coded scenarios would not be feasible. Conclusions : Most cases coded as OI or OU could be recoded as one of the NPDS predefined therapeutic error scenarios or non-error reasons for exposure. Considering the large proportion of double dose cases and the unique errors associated with mistaken strengths of tablets, these scenarios could be appropriate to add as new predefined coding scenarios, which would aid in future research and patient counseling.