Delta-8 tetrahydrocannabinol, delta-10 tetrahydrocannabinol, and tetrahydrocannabinol-O acetate exposures reported to America's Poison Centers.

INTRODUCTION: Since the passage of the Farm Bill in 2018, the availability of synthetic tetrahydrocannabinols has increased, including delta-8 tetrahydrocannabinol, delta-10 tetrahydrocannabinol, and tetrahydrocannabinol-O acetate. The objective of this study is to investigate the characteristics of delta-8 tetrahydrocannabinol, delta-10 tetrahydrocannabinol, and tetrahydrocannabinol-O acetate exposures reported to United States poison centers from 2021 to 2022. METHODS: National Poison Data System data were analyzed, including year, individual demographics, substance category and type, reason for exposure, highest level of health care received, and medical outcome. United States Census Bureau data were used to calculate population-based rates. RESULTS: There were 5,022 reported cases involving delta-8 tetrahydrocannabinol, delta-10 tetrahydrocannabinol, and tetrahydrocannabinol-O acetate as the primary substance reported to United States poison centers from 1 January 2021 to 31 December 2022. The rate of exposure per 100,000 United States population increased by 89.1 percent from 0.55 in 2021 to 1.04 in 2022. Children less than 6 years old accounted for 30.1 percent of cases, with a mode at age 2 years (representing 8.9 percent of cases). Most cases involved delta-8 tetrahydrocannabinol (98.1 percent), were single-substance exposures (94.3 percent), or occurred in a residence (95.9 percent). Ingestions accounted for 94.2 percent of cases, including 95.1 percent among children less than 6 years old. The leading reason for exposure was unintentional-general (40.2 percent), followed by abuse (33.1 percent). The most common related clinical effects were mild central nervous system depression (25.0 percent), tachycardia (23.0 percent), and agitation (15.6 percent). More than one-third (38.4 percent) of cases experienced a serious medical outcome, and 10.3 percent were admitted to a noncritical care unit and 5.3 percent to a critical care unit. DISCUSSION AND LIMITATIONS: The National Poison Data System is limited by its passive surveillance design. Delta-8 tetrahydrocannabinol, delta-10 tetrahydrocannabinol, and tetrahydrocannabinol-O acetate have toxic effects, and reports to United States poison centers increased from 2021 to 2022. Unintentional ingestions by young children are of particular concern. CONCLUSIONS: Opportunities exist to improve regulation, with accompanying enforcement, of these products and to educate the public about their potential toxicity.

Glucagon-Like Peptide-1 Receptor Agonist Cases Reported to United States Poison Centers, 2017-2022.

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a class of medications for management of diabetes and obesity. The objective of this study is to characterize the epidemiology of GLP-1RA cases reported to US poison centers. METHODS: We analyzed cases involving a GLP-1RA reported to the National Poison Data System during 2017-2022. RESULTS: There were 5,713 single-substance exposure cases reported to US poison centers involving a GLP-1RA. Most cases were among females (71.3%) and attributable to therapeutic errors (79.9%). More than one-fifth (22.4%) of cases were evaluated in a healthcare facility, including 0.9% admitted to a critical care unit and 4.1% admitted to a non-critical care unit. Serious medical outcomes were described in 6.2% of cases, including one fatality. The rate of cases per one million US population increased from 1.16 in 2017 to 3.49 in 2021, followed by a rapid increase of 80.9% to 6.32 in 2022. Trends for rates of serious medical outcomes and admissions to a healthcare facility showed similar patterns with 129.9% and 95.8% increases, respectively, from 2021 to 2022. CONCLUSIONS: Most GLP-1RA cases reported to US poison centers were associated with no or minimal effects and did not require referral for medical treatment; however, a notable minority of individuals experienced a serious medical outcome or healthcare facility admission. The rate of reported cases increased during the study period, including an 80.9% increase from 2021 to 2022. Opportunities exist to improve provider and patient awareness of the adverse effects of these medications.

Evaluation of the relationship of xylazine and fentanyl blood concentrations among fentanyl-associated fatalities.

INTRODUCTION: Illicit fentanyl and fentanyl-analogs have produced a devastating increase in opioid fatalities in the United States. Increasingly, xylazine has been found in the illicit fentanyl supply. The role of xylazine in fentanyl intoxication remains unclear. We reviewed coroner records to evaluate trends and effects associated with xylazine in fentanyl-related fatalities. METHODS: This is a retrospective cohort study of all deaths reported to the Franklin County Coroner's Office in Ohio from 1 January 2019 to 16 March 2023, in which fentanyl was determined causative or contributory to death. Cases identified as fentanyl-associated fatalities were separated into two groups based on whether or not xylazine was also detected. RESULTS: There were 3,052 fentanyl-related fatalities during the study period. 4.8 percent of these decedents also tested positive for xylazine. There was no meaningful demographic difference between fentanyl-related fatalities in which xylazine was detected versus those without xylazine detected. There was a mean of 726 fentanyl-associated fatalities per year, with a peak of 846 deaths in 2020 and a decline thereafter. The percentage of fentanyl-related fatalities with xylazine detected increased in linear fashion from 2.7 percent in 2019 to 6.6 percent in 2022. The median fentanyl concentration was 17.0 µg/L (inter-quartile range: 7.9, 27.0) in cases with xylazine detected and 10.0 µg/L (inter-quartile range: 5.6, 18.0) without xylazine. The odds of a fentanyl concentration greater than 40 µg/L in cases with xylazine detected was more than twice as great (odds ratio: 2.41; 95 percent confidence interval: 1.58-3.64) than that in cases without xylazine detected. CONCLUSIONS: Postmortem fentanyl concentrations were greater in cases with xylazine detected than those without xylazine detected. Though it is unclear why patients who were exposed to xylazine tolerated higher opioid doses prior to succumbing to death, we postulate that xylazine may act to competitively antagonize some degree of mu-opioid receptor binding by opioids.

Loperamide cases reported to United States poison centers, 2010-2022.

BACKGROUND: Intentional use of high doses of loperamide has been linked to serious cardiac toxicity. The objective of this study is to investigate the characteristics and trends of loperamide cases reported to United States (US) poison centers and to evaluate the changes in reported loperamide cases following US Food and Drug Administration (FDA) warnings, labeling requirements, and packaging restrictions for loperamide starting in 2016, with an emphasis on intentional exposures. METHODS: Data from the National Poison Data System were analyzed. RESULTS: There were 12,987 cases reported to US poison centers from 2010 to 2022, for which, loperamide was the most likely substance responsible for observed clinical effects. Although 46.1% of these cases were associated with minor or no effect, 13.4% resulted in a serious medical outcome, including 59 deaths (0.5%). Eight percent (8.1%) of cases were admitted to a critical care unit and 5.0% were admitted to a non-critical care unit. Among cases with a serious medical outcome, most were associated with loperamide abuse (38.0%), intentional-misuse (15.7%), or suspected suicide (27.5%). The majority (60.0%; n = 33) of fatalities were related to abuse, followed by suspected suicide (20.0%; n = 11) and intentional-misuse (5.5%, n = 3). The rate of loperamide cases per 100,000 US population reported to US PCs decreased from 0.44 in 2010 to 0.36 in 2015 (p = 0.0290), followed by an increase to 0.46 in 2017 (p = 0.0013), and then a trend reversal with a decrease to 0.28 in 2022 (p < 0.0001). The rate of serious medical outcomes related to loperamide increased from 0.03 in 2010 to 0.05 in 2015 (p = 0.0109), which subsequently increased rapidly to 0.11 in 2017 (p < 0.0001), and then demonstrated a trend reversal and decreased to 0.04 in 2022 (p < 0.0001). CONCLUSIONS: FDA warnings, labeling requirements, and packaging restrictions may have contributed to the observed trend reversal and decrease in reports to US poison centers of loperamide cases related to intentional misuse, abuse, and suspected suicide. This demonstrates the potential positive effect that regulatory actions may have on public health. These findings contribute to the evidence supporting the application of similar prevention efforts to reduce poisoning from other medications associated with intentional misuse, abuse, and suicide.

Pediatric extracorporeal cardiopulmonary resuscitation for yew cardiotoxicity.

INTRODUCTION: English yew is an evergreen conifer frequently planted in household gardens and, when ingested in large doses, results in severe cardiotoxicity characterized by difficult to control ventricular arrhythmias with high rates of mortality. CASE REPORT: A previously healthy teenage female presented as an out-of-hospital cardiac arrest with refractory ventricular arrhythmias and severe biventricular dysfunction. Due to rapid deterioration in her clinical status, she was cannulated onto venoarterial extracorporeal membrane oxygenation (ECMO) which resulted in rapid normalization of her rhythm and ventricular function. DISCUSSION: Our case highlights the importance of keeping a broad differential diagnosis when considering etiologies of ventricular arrhythmias in the pediatric population. The final diagnosis was not made until after discharge and implantable cardiac defibrillator (ICD) placement. CONCLUSION: The delayed diagnosis of this intentional English yew ingestion ultimately resulted subsequent ICD removal. Early ECMO activation in cases of English yew toxicity can be essential for patient survival.

Should Clinicians Prescribe Non-FDA Regulated Dietary Supplements When Caring for Children With Hypovitaminosis D?

Hypovitaminosis D is a prevalent micronutrient deficiency that can be severe and hard to treat in children with short bowel syndrome, a condition treated with substantial bowel resection. Surgically altered bowel anatomy then results in iatrogenic digestion and absorption limitations that require short- and long-term management and follow-up. Care of children with hypovitaminosis D standardly includes prescription dietary micronutrient supplementation, sometimes in irregularly high doses. This commentary responds to a pediatric case of vitamin D toxicity and suggests micronutrient-prescribing risk mitigation strategies in light of the absence of regulatory oversight of over-the-counter dietary supplements, inadequate insurance coverage, and easily available commercial retail products.

Magnet Injuries in Children: An Analysis of the National Poison Data System from 2008 to 2019.

OBJECTIVE: To examine, using the National Poison Data System (the data warehouse for poison control centers in the US), magnet foreign body injuries in pediatric patients. We sought to report demographic data, outcome data, and case trends between 2008 and 2019. STUDY DESIGN: We conducted a retrospective analysis of the National Poison Data System for patients younger than 19 years of age with a magnet "exposure," which poison centers define as an ingestion, inhalation, injection, or dermal exposure to a poison. RESULTS: A total of 5738 magnet exposures were identified. Most were male (3169; 55%), <6 years old (3572; 62%), with an unintentional injury (4828; 84%). There were 222 patients (3.9%) with a confirmed medical "effect," defined as signs, symptoms, and clinical findings not including therapeutic interventions (eg, endoscopy). There was a 33% decrease in cases from 418 (2008-2011) to 281 per year (2012-2017) after high-powered magnet sets were removed from the market. Calls subsequently increased 444% to 1249 per year (2018-2019) after high-powered magnet sets re-entered the market. Cases from 2018 and 2019 increased across all age groups and account for 39% of magnet cases since 2008. CONCLUSIONS: Significant increases in magnet injuries correspond to time periods in which high-powered magnet sets were sold, including a 444% increase since 2018. These results reflect the increased need for preventative or legislative efforts.

Cleaning and Disinfectant Chemical Exposures and Temporal Associations with COVID-19 - National Poison Data System, United States, January 1, 2020-March 31, 2020.

On January 19, 2020, the state of Washington reported the first U.S. laboratory-confirmed case of coronavirus disease 2019 (COVID-19) caused by infection with SARS-CoV-2 (1). As of April 19, a total of 720,630 COVID-19 cases and 37,202 associated deaths* had been reported to CDC from all 50 states, the District of Columbia, and four U.S. territories (2). CDC recommends, with precautions, the proper cleaning and disinfection of high-touch surfaces to help mitigate the transmission of SARS-CoV-2 (3). To assess whether there might be a possible association between COVID-19 cleaning recommendations from public health agencies and the media and the number of chemical exposures reported to the National Poison Data System (NPDS), CDC and the American Association of Poison Control Centers surveillance team compared the number of exposures reported for the period January-March 2020 with the number of reports during the same 3-month period in 2018 and 2019. Fifty-five poison centers in the United States provide free, 24-hour professional advice and medical management information regarding exposures to poisons, chemicals, drugs, and medications. Call data from poison centers are uploaded in near real-time to NPDS. During January-March 2020, poison centers received 45,550 exposure calls related to cleaners (28,158) and disinfectants (17,392), representing overall increases of 20.4% and 16.4% from January-March 2019 (37,822) and January-March 2018 (39,122), respectively. Although NPDS data do not provide information showing a definite link between exposures and COVID-19 cleaning efforts, there appears to be a clear temporal association with increased use of these products.

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.

Characterization of drug overdoses in an Ohio incarcerated population.

CONTEXT: Literature exists about drug overdose following release of recently incarcerated individuals and mortality among prisoners in the United States, but little information exists about drug overdoses in the imprisoned population. OBJECTIVE: This study aims to quantify and describe prisoner medication overdose requiring inpatient admission or assessment at a tertiary care facility and to assess the associated hospital charges. MATERIALS AND METHODS: A single-center, retrospective cohort study was conducted on all Ohio Department of Rehabilitation and Correction inmates who presented to The Ohio State University Wexner Medical Center with drug overdose between 15 October 2011 and 14 October 2014. Demographic information, overdose substances, exposure reason, clinical effects, lengths of stay, outcomes, and hospital charges were collected. RESULTS: Of the 130 patients included in the study, there were 100 intentional overdoses, 7 unintentional overdoses, 3 adverse drug reactions, and 20 unknown intentions. The most common drug in prisoner overdose was phenytoin (n = 29, 22%). While anticonvulsants were the most common drug class overall, anticonvulsants, antidepressants, and cardiovascular medications accounted for equal numbers of intensive care unit (ICU) admissions. Most patients exhibited multiple symptoms on arrival, most commonly neurologic, cardiovascular, and gastrointestinal symptoms. Patients were seen from 21 of the 28 Ohio Department of Rehabilitation and Correction facilities, of which five facilities, that largely house minimum and medium security prisoners, accounted for 61% of patients sent to our institution. The total sum of charges was $2,606,942 with 55% of charges from ICU stays. CONCLUSION: Our study shows that drug overdoses within our incarcerated population were largely intentional overdoses of anticonvulsants, cardiovascular drugs, and antidepressants. Opportunities exist to target intentional drug overdoses that accounted for 80% of prisoner overdoses for potential cost-savings.

Fluoropolymer-associated illness.

CONTEXT: Isolated outbreaks of respiratory illness associated with fluoropolymer-containing products, such as waterproofing agents and sealants, have occurred for many years in many different countries. Despite this, an assured mechanism of illness is not defined, representing a barrier to the prevention of future occurrences. OBJECTIVE: To discuss the epidemiology of the respiratory illness outbreaks, proposed mechanisms of toxicity and clinical outcomes from exposure to these products. METHODS: We performed a literature review using OVID Medline (January 1946 through December 2012) and PubMed (January 1950 through December 2012) using the search terms "fluoropolymer", "fluorochemical", "leather proofing", "leather protectant", "weatherproofing agent", and "waterproofing agent". Bibliographies of identified articles were screened for additional relevant studies, including non-indexed reports. RESULTS: Fluoropolymer-associated respiratory illnesses often resemble polymer fume fever: acute respiratory symptoms predominate and are accompanied by flu-like symptoms. Outbreaks occasionally follow marketing of a new or reformulated product. Treatment with basic and supportive measures is sufficient in many cases, including fresh air and supplemental oxygen. Inhaled beta-2 adrenergic agonists and corticosteroids have been used. Toxicity may result from the fluoropolymer itself or the solvent in which it is delivered. Factors which may influence toxicity include fluoropolymer particle size, emission rate, methods of application, environmental conditions, and personal health. CONCLUSION: Exposure to fluoropolymer-containing waterproofing agents can cause lung injury and usually produce abrupt onset of respiratory and flu-like symptoms. Most victims improve with supportive care and supplemental oxygen. Serious outcomes, including acute respiratory distress syndrome and death, are uncommon. Proprietary information on the exact composition of most fluoropolymer-containing products is often unavailable, and this hinders identification of an exact cause of disease. The etiology is most likely multifactorial. Future research should focus on determining the exact mechanism of illness and establishing safe exposure limits.

Thyrotoxicosis after a massive levothyroxine ingestion in a 3-year-old patient.

Most children with exploratory levothyroxine ingestions remain asymptomatic or suffer only minor effects, and most patients can be managed in the home or with supportive care in the hospital. We present a case of a 3-year-old girl who was found after a witnessed massive ingestion of levothyroxine. The patient was initially seen in an emergency department and discharged in stable condition, only to return 4 days after ingestion with thyrotoxicosis, hypertension, tachycardia, 24 hours of persistent vomiting, and clinical and laboratory evidence of dehydration. On the day of hospital admission, her thyroid-stimulating hormone was 0.018 µIU/mL (reference range, 0.6-4.5 µIU/mL); free T4 (tetraiodothyronine) was greater than 6.0 ng/dL (reference range, 0.7-2.1 ng/dL); and T3 (triiodothyronine) total was 494 ng/dL (reference range, 100-200 ng/dL). During a 3-day hospital admission, she was managed with supportive care, including intravenous fluid rehydration and antiemetics, and was ultimately discharged in good condition. The patient was followed up until 2 months after ingestion and remained asymptomatic. Although most exploratory levothyroxine ingestions suffer little to no clinical effects, serious symptoms can occur. Because serious symptoms can occur in a delayed fashion, it is important for clinicians to give proper anticipatory guidance regarding home symptom monitoring, follow-up, and reasons to return to the emergency department when patients present for medical evaluation.

Overdose of drugs for attention-deficit hyperactivity disorder: clinical presentation, mechanisms of toxicity, and management.

The prevalence of attention-deficit hyperactivity disorder (ADHD) in the USA is estimated at approximately 4-9% in children and 4% in adults. It is estimated that prescriptions for ADHD medications are written for more than 2.7 million children per year. In 2010, US poison centers reported 17,000 human exposures to ADHD medications, with 80% occurring in children <19 years old and 20% in adults. The drugs used for the treatment of ADHD are diverse but can be roughly separated into two groups: the stimulants such as amphetamine, methylphenidate, and modafinil; and the non-stimulants such as atomoxetine, guanfacine, and clonidine. This review focuses on mechanisms of toxicity after overdose with ADHD medications, clinical effects from overdose, and management. Amphetamine, dextroamphetamine, and methylphenidate act as substrates for the cellular monoamine transporter, especially the dopamine transporter (DAT) and less so the norepinephrine (NET) and serotonin transporter. The mechanism of toxicity is primarily related to excessive extracellular dopamine, norepinephrine, and serotonin. The primary clinical syndrome involves prominent neurological and cardiovascular effects, but secondary complications can involve renal, muscle, pulmonary, and gastrointestinal (GI) effects. In overdose, the patient may present with mydriasis, tremor, agitation, hyperreflexia, combative behavior, confusion, hallucinations, delirium, anxiety, paranoia, movement disorders, and seizures. The management of amphetamine, dextroamphetamine, and methylphenidate overdose is largely supportive, with a focus on interruption of the sympathomimetic syndrome with judicious use of benzodiazepines. In cases where agitation, delirium, and movement disorders are unresponsive to benzodiazepines, second-line therapies include antipsychotics such as ziprasidone or haloperidol, central alpha-adrenoreceptor agonists such as dexmedetomidine, or propofol. Modafinil is not US FDA approved for treatment of ADHD; however, it has been shown to improve ADHD signs and symptoms and has been used as an off-label pharmaceutical for this diagnosis in both adults and children. The mechanism of action of modafinil is complex and not fully understood. It is known to cause an increase in extracellular concentrations of dopamine, norepinephrine, and serotonin in the neocortex. Overdose with modafinil is generally of moderate severity, with reported ingestions of doses up to 8 g. The most common neurological effects include increased anxiety, agitation, headache, dizziness, insomnia, tremors, and dystonia. The management of modafinil overdose is largely supportive, with a focus on sedation, and control of dyskinesias and blood pressure. Atomoxetine is a selective presynaptic norepinephrine transporter inhibitor. The clinical presentation after overdose with atomoxetine has generally been mild. The primary effects have been drowsiness, agitation, hyperactivity, GI upset, tremor, hyperreflexia, tachycardia hypertension, and seizure. The management of atomoxetine overdose is largely supportive, with a focus on sedation, and control of dyskinesias and seizures. Clonidine is a synthetic imidazole derivative with both central and peripheral alpha-adrenergic agonist actions. The primary clinical syndrome involves prominent neurological and cardiovascular effects, with the most commonly reported features of depressed sensorium, bradycardia, and hypotension. While clonidine is an anti-hypertensive medication, a paradoxical hypertension may occur early with overdose. The clinical syndrome after overdose of guanfacine may be mixed depending on central or peripheral alpha-adrenoreceptor effects. Initial clinical effects may be drowsiness, lethargy, dry mouth, and diaphoresis. Cardiovascular effects may depend on time post-ingestion and may present as hypotension or hypertension. The management of guanfacine overdose is largely supportive, with a focus on support of blood pressure. Overdose with ADHD medications can produce major morbidity, with many cases requiring intensive care medicine and prolonged hospital stays. However, fatalities are rare with appropriate care.