2023 American Heart Association Focused Update on the Management of Patients With Cardiac Arrest or Life-Threatening Toxicity Due to Poisoning: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.

In this focused update, the American Heart Association provides updated guidance for resuscitation of patients with cardiac arrest, respiratory arrest, and refractory shock due to poisoning. Based on structured evidence reviews, guidelines are provided for the treatment of critical poisoning from benzodiazepines, ß-adrenergic receptor antagonists (also known as ß-blockers), L-type calcium channel antagonists (commonly called calcium channel blockers), cocaine, cyanide, digoxin and related cardiac glycosides, local anesthetics, methemoglobinemia, opioids, organophosphates and carbamates, sodium channel antagonists (also called sodium channel blockers), and sympathomimetics. Recommendations are also provided for the use of venoarterial extracorporeal membrane oxygenation. These guidelines discuss the role of atropine, benzodiazepines, calcium, digoxin-specific immune antibody fragments, electrical pacing, flumazenil, glucagon, hemodialysis, hydroxocobalamin, hyperbaric oxygen, insulin, intravenous lipid emulsion, lidocaine, methylene blue, naloxone, pralidoxime, sodium bicarbonate, sodium nitrite, sodium thiosulfate, vasodilators, and vasopressors for the management of specific critical poisonings.

Impact of Recreational Cannabis Legalization on Opioid Prescribing and Opioid-Related Hospital Visits in Colorado: an Observational Study.

BACKGROUND: Cannabis may be a substitute for opioids but previous studies have found conflicting results when using data from more recent years. Most studies have examined the relationship using state-level data, missing important sub-state variation in cannabis access. OBJECTIVE: To examine cannabis legalization on opioid use at the county level, using Colorado as a case study. Colorado allowed recreational cannabis stores in January 2014. Local communities could decide whether to allow dispensaries, creating variation in the level of exposure to cannabis outlets. DESIGN: Observational, quasi-experimental design exploiting county-level variation in allowance of recreational dispensaries. SUBJECTS: Colorado residents MEASURES: We use licensing information from the Colorado Department of Revenue to measure county-level exposure to cannabis outlets. We use the state's Prescription Drug Monitoring Program (2013-2018) to construct opioid-prescribing measures of number of 30-day fills and total morphine equivalents, both per county resident per quarter. We construct outcomes of opioid-related inpatient visits (2011-2018) and emergency department visits (2013-2018) with Colorado Hospital Association data. We use linear models in a differences-in-differences framework that accounts for the varying exposure to medical and recreational cannabis over time. There are 2048 county-quarter observations used in the analysis. RESULTS: We find mixed evidence of cannabis exposure on opioid-related outcomes at the county level. We find increasing exposure to recreational cannabis is associated with a statistically significant decrease in number of 30-day fills (coefficient: -117.6, p-value<0.01) and inpatient visits (coefficient: -0.8, p-value: 0.03), but not total MME nor ED visits. Counties with no medical exposure prior to recreational legalization experience greater reductions in the number of 30-day fills and MME than counties with prior medical exposure (p=0.02 for both). CONCLUSIONS: Our mixed findings suggest that further increases in cannabis beyond medical access may not always reduce opioid prescribing or opioid-related hospital visits at a population level.

Health Effects of High-Concentration Cannabis Products: Scoping Review and Evidence Map.

Background. The concentration of pharmacologically active tetrahydrocannabinol (THC) in cannabis products has been increasing over the past decade. Concerns about potential harmful health effects of using these increasingly higher-concentration products have led some states to consider regulation of cannabis product THC concentration. We conducted a scoping review of health effects of high-concentration cannabis products to inform policy on whether the THC concentrations of cannabis product should be regulated or limited. Objectives. We conducted a scoping review to (1) identify and describe human studies that explore the relationship of high-concentration cannabis products with any health outcomes in the literature and (2) create an interactive evidence map of the included studies to facilitate further analyses. Search Methods. An experienced medical information specialist designed a comprehensive search strategy of 7 electronic databases. Selection Criteria. We included human studies of any epidemiological design with no restrictions by age, sex, health status, country, or outcome measured that reported THC concentration or included a known high-concentration cannabis product. Data Collection and Analysis. We imported search results into Distiller SR, and trained coders conducted artificial intelligence‒assisted screening. We developed, piloted, and revised data abstraction forms. One person performed data abstraction, and a senior reviewer verified a subset. We provide a tabular description of study characteristics, including exposures and outcomes measured, for each included study. We interrogated the evidence map published in Tableau to answer specific questions and provide the results as text and visual displays. Main Results. We included 452 studies in the scoping review and evidence map. There was incomplete reporting of exposure characteristics including THC concentration, duration and frequency of use, and products used. The evidence map shows considerable heterogeneity among studies in exposures, outcomes, and populations studied. A limited number of reports provided data that would facilitate further quantitative synthesis of the results across studies. Conclusions. This scoping review and evidence map support strong conclusions concerning the utility of the literature for characterizing risks and benefits of the current cannabis marketplace and the research approaches followed in the studies identified. Relevance of the studies to today's products is limited. Public Health Implications. High-quality evidence to address the policy question of whether the THC concentration of cannabis products should be regulated is scarce. The publicly available interactive evidence map is a timely resource for other entities concerned with burgeoning access to high-concentration cannabis. (Am J Public Health. 2023;113(12):1332-1342. https://doi.org/10.2105/AJPH.2023.307414).

Comparison of Two-Bag Versus Three-Bag N-Acetylcysteine Regimens for Pediatric Acetaminophen Toxicity.

BACKGROUND: Acetaminophen overdose is a leading cause of liver failure, and a leading cause of pediatric poisoning requiring hospital admission. The antidote, N-acetylcysteine (NAC), is traditionally administered as a three-bag intravenous infusion. Despite its efficacy, NAC is associated with high incidence of nonallergic anaphylactoid reactions (NAARs). Adult evidence demonstrates that alternative dosing regimens decrease NAARs and medication errors (MEs). OBJECTIVES: To compare NAARs and MEs associated with two- versus three-bag NAC for acetaminophen overdose in a pediatric population. METHODS: This is a retrospective observational cohort study comparing pediatric patients who received three- versus two-bag NAC for acetaminophen toxicity. The primary outcome was incidence of NAARs. Secondary outcomes were rates of MEs and relevant hospital outcomes (length of stay [LOS], intensive care unit (ICU) admission, liver transplant, death). RESULTS: Two hundred forty-three patients met inclusion criteria (median age of 15 years): 150 (62%) three-bag NAC and 93 (38%) two-bag NAC. There was no difference in overall NAARs (p = 0.54). Fewer cutaneous NAARs were observed in the two-bag group, three-bag: 15 (10%), two-bag: 2 (2%), p = 0.02. MEs were significantly decreased with the two-bag regimen, three-bag: 59 (39%), two-bag: 21 (23%), p = 0.01. No statistical differences were observed in LOS, ICU admissions, transplant, or death. CONCLUSION AND RELEVANCE: A significant decrease in cutaneous NAARs and MEs was observed in pediatric patients by combining the first two bags of the traditional three-bag NAC regimen. In pediatric populations, a two-bag NAC regimen for acetaminophen overdose may improve medication tolerance and safety.

Cannabis legalization and cannabis-involved pregnancy hospitalizations in Colorado.

The primary objective of this study was to evaluate the association between presence of recreational cannabis dispensaries and prevalence of cannabis-involved pregnancy hospitalizations in Colorado. This was a retrospective cohort study of pregnancy-related hospitalizations co-coded with cannabis diagnosis codes in the Colorado Hospital Association from January 1, 2011, through December 31, 2018 (recreational cannabis began January 1, 2014). Our primary outcome was cannabis-involved pregnancy hospitalizations per 10 k live births per county. The primary exposure measure was county variation in the number of recreational dispensaries. We controlled for counties' baseline exposure to medical cannabis dispensaries and used Poisson regression to evaluate the association between exposure to recreational cannabis and hospitalizations. During the study period, cannabis-involved pregnancy hospitalizations increased from 429 to 1210. Mean hospitalizations per county (1.7 to 4.7) and per 10 k live births (13.2 to 55.7) increased. Overall, increasing recreational dispensaries were associated with increases in hospitalizations (1.02, CI: 1.00,1.04). When comparing counties with different densities of baseline medical cannabis market, low and high exposure counties had fewer hospitalizations than those counties with no exposure (low: IRR 0.97, CI: 0.96-0.99; high: 0.98, CI: 0.96-0.99). In Colorado, there was more than a two-fold increase in cannabis-involved pregnancy hospitalizations between 2011 and 2018. Counties with no baseline exposure to medical cannabis had a greater increase than other counties, suggesting the recreational market may influence cannabis use among pregnant individuals.

Comparison of hospital claims and poison center data to evaluate health impact of opioids, cannabis and synthetic cannabinoids.

INTRODUCTION: Over the past 10 years, opioids and cannabis have garnered significant attention due to misuse and legalization trends. Different datasets and surveillance mechanisms can lead to different conclusions the due to a variety of factors. The primary objective of this study was to compare and describe trends of opioid, cannabis, and synthetic cannabinoid-related healthcare encounters and poison center (PC) cases in Colorado, a state that has legalized cannabis. METHODS: This was a retrospective study comparing hospital claims data (Colorado Hospital Association (CHA)) and poison center cases to describe opioid, cannabis and synthetic cannabinoid-related healthcare encounters and exposures in Colorado from 2013 to 2017 using related genetic codes and International Statistical Classification of Disease codes. RESULTS: Both datasets observed increases in cannabis related encounters and exposures after recreational cannabis legalization in 2014. CHA reported an increase for cannabis-related ER visits from 14,109 in 2013 to 18,118 in 2017 while PC noted a 74.4% increase in cannabis-related cases (125 to 218). CHA inpatient visits associated with cannabis also increased (8311 in 2013 to 14,659 in 2017). On the other hand, Opioid-related exposures to the PC fell (1092 in 2013 to 971 in 2017) while both Opioid-related ER visits (8580 in 2013 to 12,928 in 2017) and inpatient visits in CHA increased (9084 in 2013 to 13,205). CONCLUSIONS: This study demonstrates the differences in surveillance methodology for concurrent drug abuse epidemics using hospital claims and PC data. Both systems provide incomplete reports, but in combination can provide a more complete picture.

Adverse Events Related to Accidental Unintentional Ingestions From Cough and Cold Medications in Children.

OBJECTIVES: Previous research has demonstrated that accidental unsupervised ingestions (AUIs) were responsible for the majority of cough and cold medication (CCM) ingestions leading to significant adverse events (AEs) in children. The objective of this analysis was to characterize the role of AUIs in the morbidity associated with CCM exposure in children. METHODS: This surveillance study collected data from 5 United States data sources from 2009 to 2016, in children younger than 6 years with an AE from an AUI involving at least 1 CCM over-the-counter pharmaceutical ingredient. An expert panel reviewed each case to determine causality. RESULTS: From 4756 total cases reviewed, 3134 (65.9%) had an AE from an AUI determined to be at least potentially related to a CCM ingredient. The majority (61.3%) of cases occurred in children aged 2 to younger than 4 years. Most exposures occurred in the child's own residence (94.9%), and 43.8% were admitted to a health care facility (22.0% to a critical care unit). Dextromethorphan and diphenhydramine, when packaged alone or in combination products, contributed to 96.0% of AUIs. The most common specific products involved were single-ingredient pediatric liquid diphenhydramine (30.1%) and single-ingredient pediatric liquid dextromethorphan (21.4%). There were 3 deaths from solid diphenhydramine formulations. CONCLUSIONS: There continues to be opportunities for the implementation of interventions to prevent AUIs of CCM in children. Additional emphasis on engineering controls, such as flow restrictors for liquid formulations targeting diphenhydramine and dextromethorphan products, represent additional opportunities to further reduce AEs from AUIs of CCM.

Fentanyl contaminated "M30" pill overdoses in pediatric patients.

BACKGROUND: Fentanyl is a high potency opioid that has become an increasingly large proportion of the illicit drug supply. Fentanyl overdoses and deaths, including in pediatric patients, has concomitantly increased. PURPOSE: To describe two cases of pediatric fentanyl overdoses via "M30" pills illicitly sold as oxycodone. BASIC PROCEDURES: Two cases of pediatric opioid toxicity reportedly from oxycodone are presented in which mass spectrometry was used to confirm fentanyl and not oxycodone exposure. MAIN FINDINGS: Both pediatric patients required naloxone and admission to the intensive care unit following exposure. Both had urine drug screens that did not show the presence of opioids but mass spectrometry testing confirmed fentanyl exposure. CONCLUSIONS: Providers should be aware of these illicit tablets, know not to assume they are pharmaceutical, and consider the risk they pose to pediatric patients through exploratory ingestion or misuse. Further inquiry, including social investigation, should be considered for pediatric patients presenting with reported oxycodone ingestion, especially blue "M30" pills.

Prescribing Patterns of Oral Opioid Analgesic for Acute Pain at a Tertiary Care Children's Hospital Emergency Departments and Urgent Cares.

OBJECTIVES: Despite Centers for Disease Control and Prevention guidelines on adult opioid prescribing, there is a paucity of evidence and no guidelines to inform opioid prescribing in pediatrics. To develop guidelines on pediatric prescribing, it is imperative to evaluate current practice on opioid use. The objectives were to describe prescribing patterns of opioids for acute pain at a children's hospital and to compare clinical characteristics of patients who received less or greater than 3 days. METHODS: A retrospective review of oral opioid analgesics prescribed for acute pain at a tertiary care children's hospital emergency department and urgent care from January 1, 2017, to December 31, 2017. Patients younger than 22 years who received an opioid prescription upon discharge were included. Patients with hematology/oncology or chronic pain diagnosis were excluded. RESULTS: Opioids were prescribed for a median of 2.2 days (interquartile range, 1.4-3.0 days). Most opioids were prescribed for ≤3 days (1326; 79.3%), and there were 44 (2.6%) prescriptions for >7 days. Twenty-two opioid formulations were prescribed. Single-ingredient oxycodone was the most commonly prescribed (877; 52.5%); there were 724 (43.3%) acetaminophen combination products. Common diagnoses were orthopedic (973; 58.2%), surgery/burn/trauma (195; 11.7%), and ear/nose/throat (143; 8.6%). Patients who received >3 days of opioids were younger (P < 0.001), and there was no differences in sex, ethnicity, insurance, or provider qualifications. CONCLUSIONS: Overall, prescribing patterns for the duration of opioid analgesics were ≤3 days, with a median of 2 days. There was a large range of days prescribed, with variations in prescribing characteristics among patients and providers.

Prescribing Patterns of Oral Opioid Analgesic for Long Bone Fracture at Tertiary Care Children's Hospital Emergency Departments and Urgent Cares.

OBJECTIVES: Disparities in opioid prescribing in children can lead to underprescribing and poorly controlled pain. On the contrary, unnecessary overprescribing can increase the risk for misuse, abuse, and diversion. The primary objective of this study was to compare the demographics and clinical characteristics of children with an extremity fracture who did and did not receive an opioid prescription from a tertiary care children's hospital. METHODS: This was a retrospective cohort study of children younger than 22 years with extremity fracture evaluated at a tertiary care children's hospital emergency department (ED) and surrounding satellite locations (3 EDs and 4 urgent cares), from January 1, 2017, to December 31, 2017. RESULTS: There were 3325 patients younger than 22 years who were seen for evaluation of an extremity fracture. The overall median age of patients was 8 years (interquartile range [IQR], 4-11), and 1976 (59.4%) were male. Patients with extremity fractures who received opioid analgesics were older than those who did not receive opioids (median age of 10 years [IQR, 6-13 years] vs 7 years [IQR, 4-11 years], P < 0.001). There was a significant difference found between insurance types, specifically those patients receiving Medicaid and private insurance. Patients who received opioid analgesics had a higher initial pain score (7 [IQR, 4-9] vs 5 [IQR, 2-7], P < 0.001), were more likely to have an physician (MD/DO) provider (P < 0.001), and were more likely to present to the ED (P < 0.001). CONCLUSIONS: Younger patients, patients with Medicaid insurance, patients treated by an advanced care provider, and patients who presented to an urgent care were less likely to receive opioid analgesics upon discharge. These findings demonstrate that more standardization and guidance on opioid prescribing are needed in pediatrics, to both adequately treat pain and reduce harms from overprescribing of opioid analgesics.

Illicit Drug Exposures in Young Pediatric Patients Reported to the National Poison Data System, 2006-2016.

This retrospective review of poison center calls found that there were 9122 illicit drug exposures reported in children <10 years of age between 2006 and 2016. Marijuana and methamphetamine were reported most frequently, with significant increases over the study period; methamphetamine was associated with the most deaths.

Marijuana exposures in Colorado, reported to regional poison centre, 2000-2018.

The objective was to evaluate trends in marijuana exposures reported to the Colorado regional poison centre (RPC). Human exposures cases from the Colorado RPC obtained from 1 January 2000 through 31 December 2018 using generic marijuana exposure codes. There were 2221 marijuana exposures, with an increase in exposures by 11.2 cases per year (p<0.0001). Annual cases remained steady since 2014 (p=0.22), with a 19.4% increase in 2018 compared with 2017. Since 2014, the largest increase was in children age 0-8 years (p<0.0001). Edible marijuana exposures increased by 9.6 exposures per year from 2015 to 2018 (p=0.04). After observing an increase in Colorado RPC marijuana exposure cases in 2010 and 2014, annual exposures have been stable through 2017, with the first increase in legalised recreational sales era in 2018. There are specific concerns for the paediatric population and exposures involving edibles, as these cases continue to increase.

Review of Biguanide (Metformin) Toxicity.

In the 1920s, guanidine, the active component of Galega officinalis, was shown to lower glucose levels and used to synthesize several antidiabetic compounds. Metformin (1,1 dimethylbiguanide) is the most well-known and currently the only marketed biguanide in the United States, United Kingdom, Canada, and Australia for the treatment of non-insulin-dependent diabetes mellitus. Although phenformin was removed from the US market in the 1970s, it is still available around the world and can be found in unregulated herbal supplements. Adverse events associated with therapeutic use of biguanides include gastrointestinal upset, vitamin B12 deficiency, and hemolytic anemia. Although the incidence is low, metformin toxicity can lead to hyperlactatemia and metabolic acidosis. Since metformin is predominantly eliminated from the body by the kidneys, toxicity can occur when metformin accumulates due to poor clearance from renal insufficiency or in the overdose setting. The dominant source of metabolic acidosis associated with hyperlactatemia in metformin toxicity is the rapid cytosolic adenosine triphosphate (ATP) turnover when complex I is inhibited and oxidative phosphorylation cannot adequately recycle the vast quantity of H+ from ATP hydrolysis. Although metabolic acidosis and hyperlactatemia are markers of metformin toxicity, the degree of hyperlactatemia and severity of acidemia have not been shown to be of prognostic value. Regardless of the etiology of toxicity, treatment should include supportive care and consideration for adjunct therapies such as gastrointestinal decontamination, glucose and insulin, alkalinization, extracorporeal techniques to reduce metformin body burden, and metabolic rescue.

Brief report: Characterization of marijuana use in us college students by state marijuana legalization status as reported to an online survey.

BACKGROUND AND OBJECTIVE: US college student marijuana use is the highest since 1980. The objective was to investigate use characteristics among college students. METHODS: The RADARS® System College Survey Program surveyed individuals in a university, technical or online school. This was a secondary analysis of existing data. RESULTS: Seven thousand one hundred five students were enrolled, <30% of students' perceived marijuana use a health risk. Students in medical states were more likely to use marijuana compared to non-legal states. (p < .001) Smoking and edibles were common methods of use. CONCLUSIONS: Higher reports of college student use were observed in medical states without differences in risk perception. SCIENTIFIC SIGNIFICANCE: This study further demonstrates the public health impact of marijuana legalization by comparing college study use of marijuana by state legalization status, and demonstrating high rates of use of concentrated products. These findings should be factored when determining regulations and preventative measures when legalizing marijuana. (Am J Addict 2019;28:266-269).

Lacosamide Overdose: A Case of QRS Prolongation and Seizure.

BACKGROUND: Lacosamide is a third-generation antiepileptic drug. Its likely mechanism of action is via neuronal sodium channel blockade, via a unique manner compared with other antiepileptic drugs that block sodium channels. A paucity of information exists regarding lacosamide overdosage. Lacosamide overdosage is thought to cause QRS prolongation and seizures, due to its effect of sodium channel blockade. The potential efficacy of sodium bicarbonate to reverse the effects of lacosamide has not been well studied. Furthermore, prior reports of lacosamide toxicity have occurred in the setting of concomitant polypharmacy. Thus, the isolated toxic effects of the drug have not been well elucidated. CASE REPORT: We report a case of a suspected, single-ingestion overdose on lacosamide. The patient developed signs of cardiotoxicity and seizure. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: After lacosamide overdosage, the emergency physician must be capable of acute management of subsequent lacosamide toxicity. Understanding the mechanisms of action causing toxicity due to this drug can help the clinician to anticipate the interventions that may be needed or useful to treat this potentially toxic ingestion.

Latrodectus Facies After Latrodectus Hesperus Envenomation in a Pediatric Patient.

BACKGROUND: Black widow spider (Latrodectus spp) envenomation represents the most medically significant spider envenomation in the United States, prompting more than 2500 calls to poison centers annually. The female spider, which is responsible for symptomatic envenomations, is classically described as a shiny black spider with a red hourglass-shaped marking on the ventral abdomen. Clinical features of envenomation include painful muscle cramping, abdominal pain, and autonomic disturbances, such as tachycardia, hypertension, and diaphoresis. "Latrodectus facies" or "facies latrodectismica" is an additional distinctive but rarely described clinical finding characterized by periorbital edema, lacrimation, and blepharospasm. CASE REPORT: A 6-year-old female developed the typical clinical features of Latrodectus envenomation after being found in bed with a Western black widow spider (Latrodectus hesperus) with no ventral marking. She initially improved with opioid analgesia, but 6 h later her symptoms worsened again, and concurrent with this worsening she developed Latrodectus facies. She received additional opioid analgesia and all her symptoms resolved within 24 h. Her mother provided informed and written consent for the acquisition and publication of the facial photographs presented. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: A high degree of clinical suspicion is necessary to correctly diagnose Latrodectus envenomation, especially when the spider escapes unnoticed or in young children in whom the bite is not witnessed. To our knowledge, Latrodectus facies has not been reported previously in a young child, and recognition of this finding will aid clinicians in limiting unnecessary interventions and administering appropriate therapy.

Novel Drugs of Abuse.

Novel drugs of abuse are synthetic illicit drugs, or analogues of known illicit drugs, that can be more potent. Novel drugs of abuse are often labeled as designer drugs, research chemicals, legal highs, or psychoactive substances. They are often sold as designated legal or nondrug products, such as incense, plant food, or bath salts, with labeling such as "Not for Human Consumption" or "For Use in Research Only." The prevalence of use of novel drugs of abuse is difficult to determine because specific drugs, compounds, and availability of these drugs are constantly evolving. Changes in chemical structures lead to heterogeneity in physiologic response and clinical symptoms, even within the same category of drug. Pediatricians and emergency medicine physicians should be knowledgeable about novel drugs of abuse and their resulting symptoms for prevention and identification of their use.

Common Substances of Abuse.

Adolescent substance abuse remains common, with almost a third of adolescents admitting to ethanol use, and a quarter admitting to illicit drug use. It is essential for pediatricians to regularly screen adolescent patients for substance use, because early initiation of drug use has been associated with physical, behavioral, and social health risks. Adolescents abuse what is common and readily available; this includes ethanol, over-the-counter products, marijuana, and inhalants. The most common and effective clinical treatments for significant toxicity from substances of abuse is symptomatic and supportive care including hemodynamic support, respiratory support, and sedation to control psychomotor agitation.