Management of Acetaminophen Poisoning in the US and Canada: A Consensus Statement.

Importance: The US and Canada currently have no formal published nationwide guidelines for specialists in poison information or emergency departments for the management of acetaminophen poisoning, resulting in significant variability in management. Objective: To develop consensus guidelines for the management of acetaminophen poisoning in the US and Canada. Evidence Review: Four clinical toxicology societies (America's Poison Centers, American Academy of Clinical Toxicology, American College of Medical Toxicology, and Canadian Association of Poison Control Centers) selected participants (n = 21). Led by a nonvoting chairperson using a modified Delphi method, the panel created a decision framework and determined the appropriate clinical management of a patient with acetaminophen poisoning. Unique to this effort was the collection of guidelines from most poison centers in addition to systematic collection and review of the medical literature. Comments from review by external organizations were incorporated before the guideline was finalized. The project began in March 2021 and ended in March 2023. Findings: The search retrieved 84 guidelines and 278 publications. The panel developed guidelines for emergency department management of single or repeated ingestion of acetaminophen. In addition, the panel addressed extended-release formulation, high-risk ingestion, coingestion of anticholinergics or opioids, age younger than 6 years, pregnancy, weight greater than 100 kg, and intravenous acetaminophen use. Differences from current US practice include defining acute ingestion as an ingestion presentation from 4 to 24 hours after overdose was initiated. A revised form of the Rumack-Matthew nomogram was developed. The term massive ingestion was replaced with the term high-risk ingestion and denoted by a specific nomogram line. Other recommendations include specific criteria for emergency department triage, laboratory evaluation and monitoring parameters, defining the role of gastrointestinal decontamination, detailed management of acetylcysteine treatment, associated adverse effects, and stopping criteria for acetylcysteine treatment, as well as criteria for consultation with a clinical toxicologist. Finally, specific treatment considerations, including acetylcysteine dosing, fomepizole administration, and considerations for extracorporeal elimination and transplant evaluation, were addressed. Conclusions and Relevance: This qualitative study provides a consensus statement on consistent evidence-based recommendations for medical, pharmacy, and nursing education and practice to optimize care of patients with acetaminophen poisoning.

Clinical and electrocardiographic factors associated with adverse cardiovascular events in bupropion exposures.

INTRODUCTION: Bupropion toxicity can cause cardiogenic shock, ventricular dysrhythmias, and death. Clinical and electrocardiographic factors associated with adverse cardiovascular events in bupropion toxicity have not been well-studied. This study aimed to identify factors associated with adverse cardiovascular events in adult patients with isolated bupropion exposures. METHODS: This retrospective cohort study queried the National Poison Data System from 2019 through 2020. We included patients 20 years or older with acute or acute-on-chronic single-agent bupropion exposures evaluated in a healthcare facility. Exclusion criteria were confirmed non-exposure, withdrawal as a reason for exposure, lack of follow-up, documentation that exposure was probably not responsible for the effects, and missing data. The primary outcome was adverse cardiovascular events, defined as the presence of any of the following: vasopressor use, ventricular dysrhythmia, myocardial injury, or cardiac arrest. Independent variables were age, the intentionality of exposure, seizures, tachycardia, QRS widening, and QTc prolongation. Multivariable logistic regression was performed to test for independent associations between independent variables and adverse cardiovascular events. RESULTS: Of 4,640 patients included in the final analysis (56.7% female, 56.5% suspected suicidal intent), 68 (1.47%) experienced an adverse cardiovascular event. Age (odds ratio 1.03; 95% confidence intervals 1.02-1.05), single seizure (odds ratio 9.18; 95% confidence intervals 4.24-19.9) and complicated seizures (odds ratio 38.9; 95% confidence intervals 19.3-78.1), QRS widening (odds ratio 3.01; 95% confidence intervals 1.62-5.59), and QTc prolongation (odds ratio 1.76; 95% confidence intervals 1.00-3.10) were independently associated with adverse cardiovascular events. No patients with unintentional exposure experienced adverse cardiovascular events, prohibiting intentionality from inclusion in the regression model. In the post hoc subgroup analysis of intentional exposures, age, single and complicated seizures, and QRS widening remained independently associated with adverse cardiovascular events. CONCLUSIONS: Increasing age, seizures, QRS widening, and QTc prolongation were associated with adverse cardiovascular events in bupropion exposures. Adverse cardiovascular events did not occur in unintentional exposures. Further research is needed to develop screening tools and treatments for bupropion cardiotoxicity.

Intensive Care Interventions Among Children With Toxicologic Exposures to Cardiovascular Medications.

OBJECTIVES: Interventions requiring a PICU are rare in toxicologic exposures, but cardiovascular medications are high-risk exposures due to their hemodynamic effects. This study aimed to describe prevalence of and risk factors for PICU interventions among children exposed to cardiovascular medications. DESIGN: Secondary analysis of Toxicology Investigators Consortium Core Registry from January 2010 to March 2022. SETTING: International multicenter research network of 40 sites. PATIENTS: Patients 18 years old or younger with acute or acute-on-chronic toxicologic exposure to cardiovascular medications. Patients were excluded if exposed to noncardiovascular medications or if symptoms were documented as unlikely related to exposure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 1,091 patients in the final analysis, 195 (17.9%) received PICU intervention. One hundred fifty-seven (14.4%) received intensive hemodynamic interventions and 602 (55.2%) received intervention in general. Children less than 2 years old were less likely to receive PICU intervention (odds ratio [OR], 0.42; 95% CI, 0.20-0.86). Exposures to alpha-2 agonists (OR, 2.0; 95% CI, 1.11-3.72) and antiarrhythmics (OR, 4.26; 95% CI, 1.41-12.90) were associated with PICU intervention. In the sensitivity analysis removing atropine from the composite outcome PICU intervention, only exposures to calcium channel antagonists (OR, 2.12; 95% CI, 1.09-4.11) and antiarrhythmics (OR, 4.82; 95% CI, 1.57-14.81) were independently associated with PICU intervention. No independent association was identified between PICU intervention and gender, polypharmacy, intentionality or acuity of exposure, or the other medication classes studied. CONCLUSIONS: PICU interventions were uncommon but were associated with exposure to antiarrhythmic medications, calcium channel antagonists, and alpha-2 agonists. As demonstrated via sensitivity analysis, exact associations may depend on institutional definitions of PICU intervention. Children less than 2 years old are less likely to require PICU interventions. In equivocal cases, age and exposure to certain cardiovascular medication classes may be useful to guide appropriate disposition.

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.

A case report of methadone-associated hypoglycemia in an 11-month-old male.

BACKGROUND: Methadone is a synthetic µ-opioid receptor agonist that is used in the management of pain, neonatal abstinence withdrawal syndrome, and opioid dependence. Overdose can cause miosis, respiratory depression, and central nervous system depression. Rarely, hypoglycemia has been reported. We present the case of an 11-month-old male who developed hypoketotic, hyperinsulinemic, hypoglycemia after an acute, unintentional methadone exposure. CASE DETAILS: The patient was a previously healthy 11-month-old male who presented in respiratory failure. He was intubated and transferred to a large tertiary care center where his physical exam was notable for miosis. His labs were notable for a blood glucose of 17 mg/dL, an elevated insulin level, and suppressed serum beta-hydroxybutyrate. The patient was given a dextrose bolus with improvement in blood glucose. Administration of IV naloxone improved his miosis and mental status. A quantitative methadone level was sent upon arrival and was 123 ng/mL. Testing for ethanol, salicylates, sulfonylureas, and metabolic causes of hypoglycemia was negative. A fasting study showed euglycemia with suppression of insulin and appropriate ketosis. Case discussion: We present the case of an 11-month-old male who developed hypoketotic, hyperinsulinemic, hypoglycemia after an acute, unintentional methadone exposure. Alternative explanations for hypoketotic hypoglycemia were rule out. Methadone-induced hypoglycemia has been reported in cancer patients receiving methadone for pain, but a mechanism has not been identified. Based on this case, we believe that the patient's hypoglycemia was the result of methadone-induced insulin secretion. CONCLUSIONS: This case proposes that hyperinsulinism is the mechanism responsible for methadone-associated hypoglycemia. Methadone exposure should be included in the differential diagnosis of new onset hypoglycemia.

A review of the carcinogenic potential of glyphosate by four independent expert panels and comparison to the IARC assessment.

The International Agency for Research on Cancer (IARC) published a monograph in 2015 concluding that glyphosate is "probably carcinogenic to humans" (Group 2A) based on limited evidence in humans and sufficient evidence in experimental animals. It was also concluded that there was strong evidence of genotoxicity and oxidative stress. Four Expert Panels have been convened for the purpose of conducting a detailed critique of the evidence in light of IARC's assessment and to review all relevant information pertaining to glyphosate exposure, animal carcinogenicity, genotoxicity, and epidemiologic studies. Two of the Panels (animal bioassay and genetic toxicology) also provided a critique of the IARC position with respect to conclusions made in these areas. The incidences of neoplasms in the animal bioassays were found not to be associated with glyphosate exposure on the basis that they lacked statistical strength, were inconsistent across studies, lacked dose-response relationships, were not associated with preneoplasia, and/or were not plausible from a mechanistic perspective. The overall weight of evidence from the genetic toxicology data supports a conclusion that glyphosate (including GBFs and AMPA) does not pose a genotoxic hazard and therefore, should not be considered support for the classification of glyphosate as a genotoxic carcinogen. The assessment of the epidemiological data found that the data do not support a causal relationship between glyphosate exposure and non-Hodgkin's lymphoma while the data were judged to be too sparse to assess a potential relationship between glyphosate exposure and multiple myeloma. As a result, following the review of the totality of the evidence, the Panels concluded that the data do not support IARC's conclusion that glyphosate is a "probable human carcinogen" and, consistent with previous regulatory assessments, further concluded that glyphosate is unlikely to pose a carcinogenic risk to humans.