Faculty Bibliography

Likelihood ratios compare two values (i.e., case rates) in order to illustrate the magnitude of the difference between the two. This ratio increases the confidence one can have in a diagnostic test from a different vantage point than that of sensitivity and specificity. The calculations of likelihood ratios are presented along with a simplified approach. Likelihood ratios are another tool the toxicologist should employ in their understanding of statistics and probability.

INTRODUCTION/UNASSIGNED:Methylthioninium chloride is used for multiple treatment purposes and is sometimes administered through peripheral intravenous lines. We highlight the potential adverse effects of methylthioninium chloride extravasation during continuous peripheral intravenous administration. CASE SUMMARY/UNASSIGNED:A 38-year-old woman presented to the emergency department with multifactorial hypovolemic and septic shock. She was treated with a continuous peripheral infusion of intravenous methylthioninium chloride for shock refractory to multiple vasopressors. IMAGES/UNASSIGNED:One day after administration commenced, the patient developed blue staining of the left upper arm due to extravasation of methylthioninium chloride proximal to the site of infusion. Further images show its later spread. CONCLUSION/UNASSIGNED:While reported cases of methylthioninium chloride extravasation are rare, it is our preference that methylthioninium chloride should be administered through a central line in cases of continuous infusion due to the risk of potential toxicity from extravasation.

IMPORTANCE/UNASSIGNED:Sodium nitrite is a curing agent increasingly used for self-harm and suicide, and multiple locales have reported increasing cases. However, approaches to forensic investigation of these cases are not standardized, and current modes of surveillance in the United States may be inadequate. OBJECTIVE/UNASSIGNED:To define a potential standard approach for identifying sodium nitrite deaths based on forensic confirmation, and compare findings based on this standard to poison center surveillance. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This retrospective case series of sodium nitrite exposures and deaths was conducted in 2 urban medical examiner jurisdictions in New York State from 2000 to 2022. The population-based sample included individuals from (1) medical examiner reports of decedents where the cause of death was sodium nitrite and (2) poison center reports of intentional exposures to sodium nitrite. EXPOSURE/UNASSIGNED:Sodium nitrite as either cause of death (medical examiner reports) or intentional exposure (poison center reports). MAIN OUTCOMES AND MEASURES/UNASSIGNED:Medical examiner determination of sodium nitrite deaths was considered the criterion standard and relied largely on confirmatory blood nitrite testing. Poison center records were assessed for intentional exposures to sodium nitrite. RESULTS/UNASSIGNED:In this case series of 36 decendents, median (range) age was 28 (20-57) years; 23 (63.8%) were male; 6 (16.7%) were African-American, 5 (13.9%) were Chinese, 13 (36.1%) were White, and 4 (11.1%) had unknown race; and 6 (16.7%) were Hispanic. No deaths were found from 2000 to 2018, and yearly increases in deaths from 2019 to 2022; these deaths were largely missed by local poison center surveillance. Most cases (83.3% [n = 30]) had postmortem blood nitrite concentrations available, and multiple decedents had evidence of suicide kit recommendations from internet sources. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this case series of decedents in 2 New York medical examiner jurisdictions, sodium nitrite deaths increased yearly, and the medical examiners were able to obtain confirmatory nitrite concentrations in most cases. These findings suggest that poison center surveillance underestimates confirmed deaths from sodium nitrite; public health authorities should rely on multiple data sources when analyzing this problem, and forensic analyses should be standardized.

INTRODUCTION/UNASSIGNED:The use of the osmol gap as a surrogate marker of toxic alcohol poisoning is common. Unfortunately, many patients with alcoholic ketoacidosis have elevated osmol gaps and are misdiagnosed with toxic alcohol poisoning. We aimed to characterize the range of osmol gaps in patients with alcoholic ketoacidosis. METHODS/UNASSIGNED:This was a retrospective poison center study. Data from 24 years were reviewed using the following case definition of alcoholic ketoacidosis: (1) documented alcohol use disorder; (2) presence of urine or serum ketones or an elevated blood beta-hydroxybutyrate concentration; (3) an anion gap ≥14 mmol/L. Potential cases of alcoholic ketoacidosis that failed to fulfill all three criteria were adjudicated by three toxicologists. Exclusion criteria included (1) detectable toxic alcohol concentration, (2) hemodialysis and/or multiple doses of fomepizole, (3) no osmol gap documented, (4) other diagnoses that lead to a metabolic acidosis. Demographics, pH, anion gap, lactate concentration, and osmol gap were extracted. RESULTS/UNASSIGNED:Of 1,493 patients screened, 55 met criteria for alcoholic ketoacidosis. Sixty-four percent were male, and their median age was 52 years. The median osmol gap was 27 [IQR 18-36]. The largest anion gap was 57 mmol/L, and the lowest pH was 6.8. Forty-five (82%) of the patients with alcoholic ketoacidosis had osmol gaps >10; 38 (69%) had osmol gaps >20; 24 (44%) had osmol gaps >30; 11 (20%) had osmol gaps > 40. DISCUSSION/UNASSIGNED:The large range of osmol gaps in patients with alcoholic ketoacidosis often reaches values associated with toxic alcohol poisoning. The study is limited by the potential for transcribing errors and the inability to identify the cause of the osmol gap. CONCLUSIONS/UNASSIGNED:In this retrospective study, patients with alcoholic ketoacidosis had a median osmol gap of 26. Given that alcoholic ketoacidosis is easily and inexpensively treated, proper identification may prevent costly and invasive treatment directed at toxic alcohol poisoning.

A 22-kg female in early childhood with a history of reactive airway disease presented to a paediatric emergency department with acute shortness of breath, tachypnoea and wheezing. Despite treatment with albuterol and corticosteroids, her bronchospasm persisted, prompting the administration of terbutaline. The patient received 220 mcg (10 mcg/kg) terbutaline intravenously, followed immediately by an inadvertent supratherapeutic intravenous dose of 10 000 mcg (454.5 mcg/kg). The patient's laboratory results obtained minutes after the medication error were notable for: potassium, 3.1 mmol/L, lactate, 2.6 mmol/L and troponin I, 0.30 ng/mL (normal <0.03 ng/mL). Over the next 48 hours, serial serum troponin values decreased. The patient was discharged home approximately 72 hours after the initial presentation and she remained well based on follow-up calls over the next several months. Given the timing and trend of troponin concentrations, we do not believe the terbutaline overdose to be responsible for the myocardial injury.

The fourth Society for Academic Emergency Medicine (SAEM) Guidelines for Reasonable and Appropriate Care in the Emergency Department (GRACE-4) is on the topic of the emergency department (ED) management of nonopioid use disorders and focuses on alcohol withdrawal syndrome (AWS), alcohol use disorder (AUD), and cannabinoid hyperemesis syndrome (CHS). The SAEM GRACE-4 Writing Team, composed of emergency physicians and experts in addiction medicine and patients with lived experience, applied the Grading of Recommendations Assessment Development and Evaluation (GRADE) approach to assess the certainty of evidence and strength of recommendations regarding six priority questions for adult ED patients with AWS, AUD, and CHS. The SAEM GRACE-4 Writing Team reached the following recommendations: (1) in adult ED patients (over the age of 18) with moderate to severe AWS who are being admitted to hospital, we suggest using phenobarbital in addition to benzodiazepines compared to using benzodiazepines alone [low to very low certainty of evidence]; (2) in adult ED patients (over the age of 18) with AUD who desire alcohol cessation, we suggest a prescription for one anticraving medication [very low certainty of evidence]; (2a) in adult ED patients (over the age of 18) with AUD, we suggest naltrexone (compared to no prescription) to prevent return to heavy drinking [low certainty of evidence]; (2b) in adult ED patients (over the age of 18) with AUD and contraindications to naltrexone, we suggest acamprosate (compared to no prescription) to prevent return to heavy drinking and/or to reduce heavy drinking [low certainty of evidence]; (2c) in adult ED patients (over the age of 18) with AUD, we suggest gabapentin (compared to no prescription) for the management of AUD to reduce heavy drinking days and improve alcohol withdrawal symptoms [very low certainty of evidence]; (3a) in adult ED patients (over the age of 18) presenting to the ED with CHS we suggest the use of haloperidol or droperidol (in addition to usual care/serotonin antagonists, e.g., ondansetron) to help with symptom management [very low certainty of evidence]; and (3b) in adult ED patients (over the age of 18) presenting to the ED with CHS, we also suggest offering the use of topical capsaicin (in addition to usual care/serotonin antagonists, e.g., ondansetron) to help with symptom management [very low certainty of evidence].

BACKGROUND/UNASSIGNED:Prescriptions of semaglutide, a glucagon-like peptide-1 receptor agonist administered weekly for Type 2 diabetes mellitus and obesity, are increasing. Adverse effects from semaglutide overdose are poorly described. We report adverse effects from three unintentional semaglutide overdoses upon initiation. CASE REPORTS/UNASSIGNED: DISCUSSION/UNASSIGNED:These unintentional semaglutide overdoses occurred due to deficits in patient and prescriber knowledge, and evasion of regulated access to pharmaceuticals. Nonspecific gastrointestinal symptoms predominated. The potential for hypoglycemia following glucagon-like peptide-1 agonist overdose is unclear, though it did not occur in our patients. It is thought that glucagon-like peptide-1 agonists are unlikely to cause hypoglycemia because their effects are glucose-dependent and diminish as serum glucose concentrations approach euglycemia. There is, however, an increase in hypoglycemia when glucagon-like peptide-1 agonists are combined with sulfonylureas. CONCLUSIONS/UNASSIGNED:This case series highlights the critical role of patient education and training upon initiation of semaglutide therapy to minimize administration errors and adverse effects from injection of glucagon-like peptide-1 receptor agonists.

Bupropion is a substituted cathinone (β-keto amphetamine) norepinephrine/dopamine reuptake inhibitor andnoncompetitive nicotinic acetylcholine receptor antagonist that is frequently used to treat major depressive disorder. Bupropion overdose can cause neurotoxicity and cardiotoxicity, the latter of which is thought to be secondary to gap junction inhibition and ion channel blockade. We report a patient with a confirmed bupropion ingestion causing severe cardiotoxicity, for whom prophylactic veno-arterial extracorporeal membrane oxygenation (ECMO) was successfully implemented. The patient was placed on the ECMO circuit several hours before he experienced multiple episodes of hemodynamically unstable ventricular tachycardia, which were treated with multiple rounds of electrical defibrillation and terminated after administration of lidocaine. Despite a neurological examination notable for fixed and dilated pupils after ECMO cannulation, the patient completely recovered without neurological deficits. Multiple bupropion and hydroxybupropion concentrations were obtained and appear to correlate with electrocardiogram interval widening and toxicity.