Guidelines for Reasonable and Appropriate Care in the Emergency Department (GRACE-4): Alcohol use disorder and cannabinoid hyperemesis syndrome management in the emergency department.

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].

Challenges with glucagon-like peptide-1 (GLP-1) agonist initiation: a case series of semaglutide overdose administration errors.

BACKGROUND: 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: Case 1: A 53-year-old man unintentionally injected semaglutide 2 mg instead of the recommended 0.1 mg. Case 2: A 45-year-old woman unintentionally injected semaglutide 2.4 mg instead of 0.25 mg. Case 3: A 33-year-old woman injected semaglutide 1.7 mg. All three of these patients developed nonspecific gastrointestinal symptoms. No patient experienced hypoglycemia. DISCUSSION: 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: 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.

Successful Treatment of Confirmed Severe Bupropion Cardiotoxicity With Veno-Arterial Extracorporeal Membrane Oxygenation Initiation Prior to Cardiac Arrest.

Bupropion is a substituted cathinone (ß-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.

An international survey of the treatment of massive paracetamol overdose in 2023.

INTRODUCTION: Changes in the commercialization of nonprescription drugs have made large quantities of paracetamol available to individuals, resulting in larger overdoses than previously observed. Although most patients with paracetamol overdose can be managed with acetylcysteine, patients with a massive overdose may become critically ill earlier and fail standard antidotal therapy. Several strategies are proposed for the management of these patients, including using increased doses of acetylcysteine, extracorporeal removal, and fomepizole. However, the benefits of these strategies remain largely theoretical, with sparse evidence for efficacy in humans. METHODS: This cross-sectional study surveys international practice patterns of medical toxicology providers regarding the management of a hypothetical patient with a massive paracetamol overdose. RESULTS: A total of 342 responses from 31 different nations were obtained during the study period. Sixty-one percent of providers would have increased their acetylcysteine dosing when treating the hypothetical massive overdose. Thirty percent of respondents recommended an indefinite infusion of acetylcysteine at 12.5 mg/kg/hour after the bolus dose, whereas 20 percent recommended following the "Hendrickson" protocol, which advocates for a stepwise increase in acetylcysteine dosing to match high paracetamol concentrations at the 300 mg/L, 400 mg/L, and 600 mg/L lines on the Rumack-Matthew nomogram. Ten percent of respondents stated they would have given "double dose acetylcysteine" but did not specify what that entailed. Forty-seven percent of respondents indicated that they would have given fomepizole, and 28 percent of respondents recommended extracorporeal removal. DISCUSSION: Our survey study assessed the approach to a hypothetical patient with a massive paracetamol overdose and demonstrated that, at minimum, most respondents would increase the dose of acetylcysteine. Additionally, almost half would also include fomepizole, and nearly one-third would include extracorporeal removal. CONCLUSIONS: There is considerable international variation for the treatment of both non-massive and massive paracetamol overdoses. Future research is needed to identify and standardize the most effective treatment for both non-massive and massive paracetamol overdoses.

Urine Toxicology Test for Children With Altered Mental Status.

The rate of unintentional ingestion of edible cannabis products in young children is rising rapidly as laws decriminalizing both recreational and medical marijuana in the United States become more widespread.1 Cannabis poisoning in children can lead to a myriad of symptoms, most notably neurologic changes. The abrupt onset and severity of signs and symptoms after ingestion can cause diagnostic uncertainty for practitioners in the emergency department. Here, we present a case series of 5 children, 6 years of age and younger, who initially presented with altered mental status and were ultimately diagnosed with acute δ-9-tetrahydrocannabinol toxicity after cannabis ingestion confirmed by urine toxicology testing. Although urine toxicology testing is not routinely used as a diagnostic tool in pediatrics, the increasing accessibility of edible cannabis products suggests that more widespread urine toxicology testing in children with undifferentiated altered mental status is warranted.

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.

A "madd"-ening confounding: fruit seeds mimicking enteral drug concealment by computed tomography.

OBJECTIVE: To highlight the similarity between madd fruit seeds and enteral drug concealment ("body packing") on computed tomography when evaluated by Hounsfield Units. CASE REPORT: A 13-year-old girl from Senegal presented to the Emergency Department with severe abdominal pain. Examination showed right lower quadrant tenderness with rebound. Computed tomography scan of the abdomen and pelvis revealed smooth, well circumscribed, multiple intraluminal foreign bodies measuring up to 2 cm in size with Hounsfield Units measuring up to 200. The emergency department radiologist reported that these were suspicious for "body packer packets" of either opioids or cocaine, based on their appearance and Hounsfield Unit characteristics. Dietary history later revealed consuption of madd fruit (Saba senegalensis) seeds, which can cause bezoar formation and intestinal obstruction. CONCLUSION: Madd fruit seeds may appear similar to drug packets on computed tomography with similar Hounsfield Unit characteristics. History and clinical context are paramount to avoid misdiagnosis.

Induction of Labor at Term for Severe Antenatal Lead Poisoning.

INTRODUCTION: Antenatal lead exposure is associated with multiple adverse maternal and fetal consequences. Maternal blood lead concentrations as low as 10 µg/dL have been associated with gestational hypertension, spontaneous abortion, growth retardation, and impaired neurobehavioral development. Current treatment recommendations for pregnant women with a blood lead level (BLL) ≥ 45 µg/dL include chelation. We report a successful case of a mother with severe gestational lead poisoning treated with induction of labor in a term infant. CASE REPORT: A 22-year-old G2P1001 female, at 38 weeks and 5 days gestation, was referred to the emergency department for an outpatient venous BLL of 53 µg/dL. The decision was made to limit ongoing prenatal lead exposure by emergent induction as opposed to chelation. Maternal BLL just prior to induction increased to 70 µg/dL. A 3510 g infant was delivered with APGAR scores of 9 and 9 at 1 and 5 min. Cord BLL at delivery returned at 41 µg/dL. The mother was instructed to avoid breastfeeding until her BLLs decreased to below 40 µg/dL, consistent with federal and local guidelines. The neonate was empirically chelated with dimercaptosuccinic acid. On postpartum day 2, maternal BLL decreased to 36 µg/dL, and the neonatal BLL was found to be 33 µg/mL. Both the mother and neonate were discharged to an alternative lead-free household on postpartum day 4.

Confirmed Fatal Colchicine Poisoning in an Adolescent with Blood and Bile Concentrations-Implications for GI Decontamination?

INTRODUCTION: Colchicine is commonly used to treat diseases like acute gouty arthritis. However, colchicine has a very narrow therapeutic index, and ingestions of > 0.5mg/kg can be deadly. We report a fatal acute colchicine overdose in an adolescent. Blood and postmortem bile colchicine concentrations were obtained to better understand the degree of enterohepatic circulation of colchicine. CASE REPORT: A 13-year-old boy presented to the emergency department after acute colchicine poisoning. A single dose of activated charcoal was administered early but no other doses were attempted. Despite aggressive interventions such as exchange transfusion and veno-arterial extracorporeal membrane oxygenation (VA-ECMO), the patient died 8 days later. Postmortem histology was notable for centrilobular necrosis of the liver and a cardiac septal microinfarct. The patient's blood colchicine concentration on hospital days 1 (~30 hours post-ingestion), 5, and 7 was 12ng/mL, 11ng/mL, and 9.5ng/mL, respectively. A postmortem bile concentration obtained during autopsy was 27ng/mL. DISCUSSION: Humans produce approximately 600mL of bile daily. Assuming that activated charcoal would be able to adsorb 100% of biliary colchicine, using the bile concentration obtained above, only 0.0162mg of colchicine per day would be able to be adsorbed and eliminated by activated charcoal in this patient. CONCLUSION: Despite supportive care, activated charcoal, VA-ECMO, and exchange transfusion, modern medicine may not be enough to prevent death in severely poisoned colchicine patients. Although targeting enterohepatic circulation with activated charcoal to enhance elimination of colchicine sounds attractive, the patient's low postmortem bile concentration of colchicine suggests a limited role of activated charcoal in enhancing elimination of a consequential amount of colchicine.

Massive Apixaban Overdose Confirmed with Blood Concentrations and Managed Without Bleeding: A Single Case Report.

BACKGROUND: Acute overdoses of apixaban, and other direct oral anticoagulants are relatively uncommon. The number of direct oral anticoagulants prescriptions in the United States is increasing, however reports on patient outcomes after documented overdose are sparse. CASE REPORT: A 76-year-old man with a past medical history of atrial fibrillation and taking apixaban 5 mg twice daily presented to the emergency department 10 hours after reportedly ingesting 60-70 of his pills. He was alert and had a normal physical examination. Blood tests demonstrated an INR of 12, platelets of 161 000 cells/mm3, hemoglobin 9.7 g/dL, and creatinine 1.81 mg/dL. He received 60 g of activated charcoal and 4 units of fresh frozen plasma prophylactically. Initial blood apixaban concentration was 4 000 ng/mL. Repeat blood apixaban concentrations were 3 000 ng/mL and 2 200 ng/mL at 7 and 14 hours, respectively (thrapeutic range 91-321 ng/mL for a 5 mg twice daily dose). The hybrid anti-factor Xa activity did not correlate with blood apixaban concentrations. Apixaban elimination followed first-order kinetics with an apparent elimination half-life of 14 hours in the presence of impaired renal function. He did not have any minor or major bleeding events.

Massive intentional enoxaparin overdose managed with minimal protamine: A single case report.

PURPOSE: The case of a patient with a massive acute enoxaparin overdose managed with observation and minimal doses of protamine sulfate is reported. SUMMARY: Acute enoxaparin overdoses are uncommonly reported and management is widely variable. A 25-year-old man presented to the emergency department (ED) shortly after reporting that he had attempted suicide by injecting himself with 31 syringes of 80 mg of enoxaparin (a total of 2,480 mg) in the abdomen and other areas of his body. The patient also had self-inflicted superficial lacerations of the forearm. Due to concern over suspected compartment syndrome in the forearm, 25 mg of protamine was administered. Approximately 11 hours after reported enoxaparin self-injection, the patient's activated partial thromboplastin time (aPTT) was 206 seconds, prompting administration of an additional 50 mg of protamine. Three hours later, the aPTT had decreased to 79 seconds, then rose over several hours to 127 seconds before gradually declining to normal values. Protamine administration had no appreciable impact on anti-factor Xa activity. The patient did not require any blood products during the hospital admission. There were no further complications, and the patient was discharged to the inpatient psychiatry service on hospital day 8. CONCLUSION: The case highlights the role of protamine as a reversal agent in the management of low-molecular-weight heparin overdoses. The optimal dosing and efficacy of protamine for this indication needs further investigation.

Retrospective evaluation of management guidelines for extracorporeal treatment of metformin poisoning.

INTRODUCTION: The Extracorporeal Treatments in Poisoning (EXTRIP) Workgroup defined criteria for extracorporeal toxin removal in patients with metformin poisoning. The primary objective of this study was to determine the benefit of extracorporeal toxin removal in patients meeting EXTRIP criteria. The secondary objective was to determine the performance characteristics of the EXTRIP criteria. METHODS: This was a single-center retrospective analysis of metformin poisoned patients. Inclusion criteria were: suspicion of metformin poisoning with at least one of the following present: lactate concentration >5 mmol/L; pH < 7.35; or impaired kidney function. Patient data were extracted by reviewers who were unaware of the study hypothesis. Cases were analyzed based on EXTRIP criteria, whether extracorporeal toxin removal was performed, and survival. Sensitivity, specificity, negative predictive value and positive predictive value were calculated with respect to the EXTRIP criteria and survival. RESULTS: Of 201 patients studied, 145 patients met recommended EXTRIP criteria (EXTRIP positive) and 56 patients did not (EXTRIP negative). Among patients who met recommended EXTRIP criteria, 96 received extracorporeal toxin removal and 49 did not. There was no difference in survival between these groups: 75.0% versus 73.5%, respectively (P >0.05). All 56 patients who did not meet EXTRIP criteria, survived (negative predictive value = 100%). DISCUSSION: The study did not demonstrate a survival benefit for extracorporeal toxin removal in those meeting EXTRIP criteria. CONCLUSION: In this retrospective analysis, the recommended EXTRIP criteria had a negative predictive value for death of 100%. Further study is needed to evaluate the benefit of extracorporeal toxin removal in patients meeting EXTRIP criteria for metformin poisoning.

Neurologic and Thrombotic Complications in the Setting of Chronic Nitrous Oxide Abuse.

Nitrous oxide is a commonly used inhaled anesthetic for medical procedures, as well as a drug of abuse throughout the world. Excessive nitrous oxide inhalation has been shown to cause a functional vitamin B12 deficiency and hyperhomocysteinemia, which can lead to peripheral neuropathy and hypercoagulability, respectively. While the development of neurologic toxicity from chronic nitrous oxide abuse (i.e., encephalopathy, myelopathy, and neuropathy) has been previously described, the thrombotic potential of chronic nitrous oxide abuse is less known. The authors report two cases of nitrous oxide abuse leading to both neurologic and thrombotic complications.