Resource utilization among children presenting with cannabis poisonings in the emergency department.

BACKGROUND: Exploratory pediatric cannabis poisonings are increasing. The aim of this study is to provide a national assessment of the frequency and trends of diagnostic testing and procedures in the evaluation of pediatric exploratory cannabis poisonings. METHODS: This is a retrospective cross-sectional study of the Pediatric Health Information Systems database involving all cases of cannabis poisoning for children age 0-10 years between 1/2016 and 12/2021. Cannabis poisoning trends were assessed using a negative binomial regression model. A new variable named "ancillary testing" was created to isolate testing that would not confirm the diagnosis of cannabis poisoning or be used to exclude co-ingestion of acetaminophen or aspirin. Ancillary testing was assessed with regression analyses, with ancillary testing as the outcomes and year as the predictor, to assess trends over time. RESULTS: A total of 2001 cannabis exposures among 1999 children were included. Cannabis exposures per 100,000 ED visits increased 68.7% (95% CI, 50.3, 89.3) annually. There was a median of 4 (IQR 2.0, 6.0) diagnostic tests performed per encounter. 64.5% of encounters received blood tests, 28.8% received a CT scan, and 2.4% received a lumbar puncture. Compared to White individuals, Black individuals were more likely to receive ancillary testing (OR 1.52 [95% CI, 1.23, 1.89]). Compared to those 2-6 years, those <2 years were more likely to receive ancillary testing (OR 1.55 [95% CI, 1.19, 2.02). We found no significant annual change in the odds of receiving ancillary testing (OR 1.04 [95% CI, 0.97, 1.12]). CONCLUSIONS: We found no change in the proportion of encounters associated with ancillary testing, despite increases in exploratory cannabis poisonings over the study period. Given the increasing rate of pediatric cannabis poisonings, emergency providers should consider this diagnosis early in the evaluation of a pediatric patient with acute change in mental status. While earlier use of urine drug screening may reduce ancillary testing and invasive procedures, even a positive urine drug screen does not rule out alternative pathologies and should not replace a thoughtful evaluation.

Pediatric hand sanitizer exposures reported to United States poison centers, 2017-2021.

INTRODUCTION: The COVID-19 pandemic increased demand for alcohol-based hand sanitizers. We aimed to describe the epidemiological trends in pediatric alcohol-based hand sanitizer cases reported to United States poison centers. We characterized clinically significant pediatric reports involving alcohol-based hand sanitizer products before and during the pandemic and methanol-containing hand sanitizers during the pandemic. METHODS: We included all single-substance cases involving alcohol-based hand sanitizers reported to the National Poison Data System among children ≤ 19 years from 1 January 2017 to 31 December 2021, and methanol-containing hand sanitizers from 23 June 2020 to 31 December 2021. Multiple product exposures and non-human exposures were excluded. Clinically significant outcomes included moderate or major effects or death. RESULTS: There were 95,718 alcohol-based hand sanitizer pediatric cases during the study period. Most (n = 89,521; 94%) were unintentional, occurred by ingestion (n = 89,879; 93.9%), occurred at home, and were managed at the exposure site (n = 89,774; 93.8%). Common symptoms were vomiting (n = 2,969; 3.1%), coughing (n = 1,102; 1.2%), ocular irritation (n = 1,244; 1.3%), and drowsiness (n = 981; 1.0%). Most children (n = 3,937; 66.2%) managed at a health care facility were treated and released; a minority were admitted (n = 527; 9.0%). Few children (n = 81; 1.4%) were admitted to the intensive care unit. The prevalence of clinically significant cases increased in 2020 and 2021, compared to 2017. Population-adjusted rates, by state, of alcohol-based hand sanitizer cases ranged from 280 to 2,700 per million children. Of the 540 reported cases involving methanol-containing hand sanitizers, the majority (n = 255) occurred in July 2020. Thirteen cases (2.4%) had clinically significant outcomes. The prevalence of clinically significant cases remained similar in 2020 and 2021 and exhibited lower prevalence compared to alcohol-based products. Population-adjusted rates, by state, ranged from fewer than 0.9 to 40 per million children. CONCLUSIONS: Clinically significant pediatric cases involving alcohol-based hand sanitizers increased during the pandemic and remained elevated in 2021. Cases involving methanol-containing products were less frequent. Our findings may inform heightened product quality control and regulatory oversight.

Association of prescription drug monitoring programs with benzodiazepine prescription dispensation and overdose in adolescents and young adults.

INTRODUCTION: Prescription drug monitoring programs are state-run databases designed to support safe prescribing of controlled substances and reduce prescription drug misuse. We analyzed healthcare claims data to determine the association between prescription drug monitoring programs with mandated provider review and adolescent and young adult benzodiazepine prescription dispensing and overdose. METHODS: We performed a state-level retrospective cohort study to evaluate the association between implementation of prescription drug monitoring programs with mandated provider review and benzodiazepine prescription dispensing and benzodiazepine-related overdoses among adolescents (13-18 years) and young adults (19-25 years) between 1 January 2008 and 31 December 2019. Data were obtained from a United States commercial health insurance company. RESULTS: There were 74,539 (1.8%) adolescents and 246,760 (4.0%) young adults with at least one benzodiazepine prescription dispensed. Benzodiazepine overdoses occurred among 1,569 (0.04%) and 3,202 (0.05%) adolescents and young adults, respectively. Implementation of a prescription drug monitoring program with mandated provider review was associated with a 6.8% (95% CI, 1.6-11.8) yearly reduction in benzodiazepine prescription dispensing among adolescents and a 12.5% (95% CI, 9.3-15.5) yearly reduction among young adults. There was no decrease in benzodiazepine overdoses in either age group (-15.4% [95% CI, -21.5 to 3.0] and -8.0% [95% CI, -18.0 to 3.2] yearly change in adolescents and young adults, respectively). DISCUSSION: Consistent with prior work, our study did not find an association between prescription drug monitoring program implementation and reduction in benzodiazepine-related overdoses among adolescents and young adults. However, the substantial reduction in benzodiazepine prescription dispensing is encouraging. CONCLUSION: Prescription drug monitoring programs were associated with decreases in benzodiazepine prescription dispensing, but not benzodiazepine-related overdoses in this cohort of adolescents and young adults. These findings serve to inform development of further policies to address rising rates of benzodiazepine misuse and overdose in this patient population.

Association of Prescription Drug Monitoring Programs With Opioid Prescribing and Overdose in Adolescents and Young Adults.

STUDY OBJECTIVE: Prescription opioid use is associated with substance-related adverse outcomes among adolescents and young adults through a pathway of prescribing, diversion and misuse, and addiction and overdose. Assessing the effect of current prescription drug monitoring programs (PDMPs) on opioid prescribing and overdoses will further inform strategies to reduce opioid-related harms. METHODS: We performed interrupted time series analyses to measure the association between state-level implementation of PDMPs with annual opioid prescribing and opioid-related overdoses in adolescents (13 to 18 years) and young adults (19 to 25 years) between 2008 and 2019. We focused on PDMPs that included mandatory reviews by providers. Data were obtained from a commercial insurance company. RESULTS: Among 9,344,504 adolescents and young adults, 1,405,382 (15.0%) had a dispensed opioid prescription, and 6,262 (0.1%) received treatment for an opioid-related overdose. Mandated PDMP review was associated with a 4.2% (95% CI, 1.9% to 6.4%) reduction in annual opioid dispensations among adolescents and a 7.8% (95% CI, 4.7% to 10.9%) annual reduction among young adults. For opioid-related overdoses, mandated PDMP review was associated with a 16.1% (95% CI, 3.8 to 26.7) and 15.9% (95% CI, 7.6 to 23.4) reduction in annual opioid overdoses for adolescents and young adults, respectively. CONCLUSION: PDMPs were associated with sustained reductions in opioid prescribing and overdoses in adolescents and young adults. Although these findings support the value of mandated PDMPs as part of ongoing strategies to reduce opioid overdoses, further studies with prospective study designs are needed to characterize the effect of these programs fully.

Trends in Dispensing of Controlled Medications for US Adolescents and Young Adults, 2008 to 2019.

This cohort study examines trends from 2008 to 2019 in dispensations of controlled medications to US adolescents and young adults.

Pediatric Melatonin Ingestions - United States, 2012-2021.

Melatonin is an endogenous neurohormone that regulates the sleep-wake cycle (1). It is used therapeutically for insomnia in adults and for primary sleep disorders in children (2). Melatonin is regulated by the Food and Drug Administration (FDA) as a dietary supplement. Various synthetic melatonin preparations are widely available over the counter (OTC) in the United States with sales increasing from $285 million in 2016 to $821 million in 2020 (3). Children are at increased risk for melatonin exposure because of the supplement's widespread use and growing popularity as a sleep aid. In 2020, melatonin became the most frequently ingested substance among children reported to national poison control centers (4); however, more research is needed to describe the toxicity and outcomes associated with melatonin ingestions in children. This study assessed isolated melatonin ingestions among the pediatric population (defined here as children, adolescents, and young adults aged ≤19 years) during January 1, 2012-December 31, 2021, using the American Association of Poison Control Centers' National Poison Data System (NPDS). During the 10-year study period, 260,435 pediatric melatonin ingestions were reported to NPDS, and the annual number of ingestions increased 530%. In addition, pediatric melatonin ingestions accounted for 4.9% of all pediatric ingestions reported to poison control centers in 2021 compared with 0.6% in 2012. Pediatric hospitalizations and more serious outcomes due to melatonin ingestions increased during the study period, primarily related to an increase in unintentional ingestions among children aged ≤5 years. Five children required mechanical ventilation, and two died. Consumers and health care professionals should be encouraged to report any melatonin product-related adverse events to MedWatch, the FDA's medical product safety reporting program. Public health initiatives should focus on raising awareness of increasing numbers of melatonin ingestions among children and on the development of preventive measures to eliminate this risk.

National assessment of anti-epileptic drug exposures among pre-teens and adolescents, 2000-2020.

BACKGROUND AND OBJECTIVES: Anti-epileptic drugs (AEDs) are increasingly used to treat psychiatric conditions, exposing many children to potentially harmful medications. This includes adolescents, who are at higher risk for self-harm. The purpose of this study was to describe the epidemiology of pediatric AED poisonings and assess which AEDs are associated with more severe clinical outcomes. METHODS: This retrospective cross-sectional analysis examined single-substance AED exposure cases in pre-teens (10-14 years) and adolescents (15-19 years) reported to the National Poison Database System (NPDS) between 2000 and 2020 (cases through 2019 were included for trend analysis due to incomplete population data). We described characteristics of ingestions by age group, including AEDs implicated. RESULTS: There were 74,818 AED exposure cases reported to the NPDS, including 25,928 (34.7%) in pre-teens and 48,890 (65.3%) in adolescents. Among adolescents, 35,570 (72.8%) exposure cases were intentional, with 27,655 (56.6%) specifically related to a suspected suicide attempt. The most common AEDs implicated in poisonings were clonazepam (19.8%), valproic acid (15.3%), and lamotrigine (13.8%). The odds of hospitalization (adjusted odds ratio [aOR] 2.0 [95% confidence interval [CI], 2.0-2.1]), intubation (aOR 2.1 [95% CI, 1.8-2.4]), seizure (aOR 1.6 [95% CI, 1.4-1.9]), and serious outcome (aOR 1.8 [95% CI, 1.7-1.9]) were higher in the adolescent group compared to the pre-teen group. Intentional ingestions increased by a yearly rate of 2.8% (95% CI, 2.3-3.2). Intentional tiagabine exposure was associated with the greatest increased odds of serious outcome (aOR 4.7 [95% CI, 3.6-6.3]). DISCUSSION: In this cross-sectional analysis of pediatric AED exposure cases reported to the NPDS, AED poisonings among pre-teens and adolescents increased significantly between 2000 and 2019. Of particular concern is the large increase in intentional exposure cases related to AEDs. With the population-adjusted rate of epilepsy diagnoses remaining relatively unchanged, these results may indicate that the rise in AED exposure cases may be related to increased prescribing of AEDs for psychiatric indications as opposed to epilepsy. CONCLUSIONS: Pediatric AED poisonings reported to the NPDS are increasing, especially among adolescents engaging in intentional ingestions. These findings provide additional information for consideration in risk-benefit assessments when selecting medications for the treatment of psychiatric conditions in children.

Clinical Effects of Pediatric Clonidine Exposure: A Retrospective Cohort Study at a Single Tertiary Care Center.

BACKGROUND: Pediatric clonidine ingestions frequently result in emergency department visits and admission for cardiac monitoring. Detailed information on the clinical course and specifically time of vital sign abnormalities of these patients is lacking. OBJECTIVE: The objective of this study was to provide descriptive analysis of the rates and times to vital sign abnormalities, treatment, disposition, and outcomes in a single-center cohort of pediatric patients with report of clonidine poisoning. METHODS: We performed a retrospective cohort study of patients younger than 21 years who presented to a large, urban, tertiary care center with a report of single substance clonidine exposure between January 2004 and November 2017. Patients were dichotomized into younger (≤9 years or younger) and older (10-21 years) groups based on the expected physiologic and psychologic differences between older and younger children. RESULTS: Eighty-eight patients met our inclusion criteria. Younger patients (≤9 years or younger; n = 47) were more likely to be exposed to someone else's medication (53%) and older patients (10-21 years; n = 41) overwhelmingly (85%) were exposed to their own medication. Thirty-nine (45%) became bradycardic, 27 (32%) became bradypneic, and 38 (44%) became hypotensive. Eighty percent of patients had depressed mental status. Thirty-three (38%) patients received at least one dose of naloxone (median 0.07 mg/kg; interquartile range 0.03-0.11 mg/kg). Of those who received naloxone, 50% had a documented clinical response. CONCLUSIONS: In this study of patients at a pediatric tertiary referral center, pediatric patients with report of clonidine exposures were likely to exhibit altered mental status and frequently develop vital sign abnormalities. Naloxone exhibited some effectiveness; given its wide safety margin, high-dose naloxone should be used in critically poisoned non-opioid-dependent patients. Because adolescents are much more likely to ingest their own clonidine medication, counseling with parents and other caregivers regarding safe medication storage is paramount.

Association of State-Level Opioid-Reduction Policies With Pediatric Opioid Poisoning.

Importance: Opioid-reduction policies have been enacted by US states to address the opioid epidemic. Evidence of an association between policy implementation and decreased rates of pediatric opioid poisoning provides further justification for expanded implementation of these policies. Objective: To examine the association of 3 state-level opioid-reduction policies with the rate of opioid poisoning in children and adolescents. Design, Setting, and Participants: This interrupted time series analysis used data from the National Poison Data System (NPDS), a database of poisoning information reported to poison control centers across the US. Individuals younger than 20 years who experienced poisoning associated with 1 or more prescription opioids from January 1, 2005, to November 30, 2017, were included. The analysis focused on 3 widespread policy interventions: the prescription drug monitoring program (PDMP), pain clinic legislation, and opioid prescribing guidelines. Data analysis was performed from January 30, 2020, to March 30, 2020. Exposures: Any opioid poisoning in individuals younger than 20 years that was reported to the NPDS. Main Outcomes and Measures: Opioid poisoning rates per million person-months before and after implementation of each of the 3 policies, overall and stratified by age (≤4 years, 5-9 years, 10-14 years, and 15-19 years). Results: A total of 338 476 opioid poisoning incidences in children and young adults were reported to the NPDS within the study period. Of this study population, the mean (SD) age was 9.74 (7.15) years, and 179 011 (52.9%) were female. The implementation of a PDMP was associated with a reduction in the monthly rate of opioid poisoning in children and adolescents (-0.07 per million person-months; 95% CI, -0.09 to -0.04) in the postimplementation period. This reduction was observed for all age groups except for the 10- to 14-year age group (-0.03 per million person-months; 95% CI, -0.05 to 0.00). Pain clinic legislation was associated with an immediate reduction in opioid poisoning (-6.22 per million person-months; 95% CI, -8.98 to -3.47). This association was statistically significant across all ages except for the 4 years or younger group. Analysis of the association of implementation of opioid prescribing guidelines was limited because of insufficient follow-up data and did not show an immediate or monthly change in the rate of opioid poisoning. Conclusions and Relevance: Results of this study suggest that certain state-level opioid-reduction policies were associated with decreases in pediatric opioid exposures across age groups. Further examination of the underlying mechanisms of these associations, including age group-specific outcomes, may expand and strengthen policies that reduce opioid poisoning, misuse, and overdoses in children and adolescents.

Myocardial Infarct After Marijuana Inhalation in a 16-year-old Adolescent Boy.

Many reports of marijuana-associated myocardial infarct (MI) are limited by incomplete evaluation of the toxicologic exposure, a lack of definitive anatomic findings, and the potential for comorbid coronary atherosclerosis inherent in an adult population. We report a 16-year-old adolescent boy who presented with chest pain after smoking marijuana and was found to have acute MI. Electrocardiogram showed diffuse ST-segment elevations. Exhaustive toxicologic testing confirmed the presence of Δ-9-tetrahydrocannabinol metabolite and ruled out other drugs of abuse. Echocardiography demonstrated moderate global left ventricular systolic dysfunction. Coronary angiography demonstrated no focal coronary lesions or obstruction. Right ventricular septal endomyocardial samples biopsied 36 hours after the onset of pain showed a subendocardial acute MI with a sparse neutrophilic infiltrate. One month after the event, magnetic resonance imaging showed a severely dilated left ventricle and moderately to severely depressed global systolic function. Late gadolinium enhancement consistent with myocardial fibrosis was seen in nearly all myocardial segments. Our unusually well-documented findings strengthen the potential association between marijuana and MI. Furthermore, we demonstrate a disease distribution supporting a process that affects the coronary circulation globally, likely at the distal, small-vessel level.

Prolonged central apnoea after intravenous morphine administration in a 12-year-old male with a UGT1A1 loss-of-function polymorphism.

ADVERSE EVENT: Repeated and prolonged episodes of central apnoea and hypoxia after receiving intravenous morphine for analgesia and ketamine for sedation. DRUG IMPLICATED: Intravenous morphine sulfate. THE PATIENT: Previously healthy 12-year-old male with no history of sleep apnoea who presented with distal tibia and fibula fracture. EVIDENCE THAT LINKS DRUG TO EVENT: Pharmacogenomic testing revealed that the patient was homozygous for the T allele at the rs887829 SNP in UGT1A1, an enzyme involved in the metabolism of morphine. This polymorphism is a loss-of-function variant, leading to impaired metabolism of morphine. MECHANISM: Morphine is metabolized by UDP-glucuronosyltransferase (UGT)-2B7 and UGT1A1 to form its major metabolites morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). Our patient was a poor metabolizer through UGT1A1, likely leading to increased respiratory depression as morphine has greater respiratory depressant effects compared to its metabolites. IMPLICATIONS: When appropriate, physicians should enquire about prior receipt of opioids, in both the patient and family, to be better prepared for potential adverse reactions. In the patient with excessive sedation or respiratory depression to standard doses of morphine, genetic testing may be warranted, especially if there is a family or past history that supports a metabolic defect in morphine metabolism and/or excretion.

Pharmacologic Treatment of Opioid Use Disorder: a Review of Pharmacotherapy, Adjuncts, and Toxicity.

Opioid use disorder continues to be a significant source of morbidity and mortality in the USA and the world. Pharmacologic treatment with methadone and buprenorphine has been shown to be effective at retaining people in treatment programs, decreasing illicit opioid use, decreasing rates of hepatitis B, and reducing all cause and overdose mortality. Unfortunately, barriers exist in accessing these lifesaving medications: users wishing to start buprenorphine therapy require a waivered provider to prescribe the medication, while some states have no methadone clinics. As such, users looking to wean themselves from opioids or treat their opioid dependence will turn to alternative agents. These agents include using prescription medications, like clonidine or gabapentin, off-label, or over the counter drugs, like loperamide, in supratherapeutic doses. This review provides information on the pharmacology and the toxic effects of pharmacologic agents that are used to treat opioid use disorder. The xenobiotics reviewed in depth include buprenorphine, clonidine, kratom, loperamide, and methadone, with additional information provided on lofexidine, akuamma seeds, kava, and gabapentin.