Use of Registries and Large Databases for Toxicology Research.

The advancement of medical toxicology knowledge has traditionally relied on case reports and case series because of the ethical challenges involved in studying poisoned patients. The growing availability of several large databases and registries now allows researchers to describe and analyze patterns in poisoned patients who share a particular exposure, outcome, or condition. A large database or registry can be useful in generating hypotheses, supporting extramural funding applications, and planning more rigorous studies. Knowing how to access and interpret data in registries such as NPDS, NHAMCS, and HCUP is essential for all stakeholders engaged in medical toxicology research. This review describes the strengths and limitations of different toxicology-relevant registries and databases and how to leverage these powerful tools to advance the science in the field of medical toxicology.

Welcome to the 2024 ACMT Annual Scientific Meeting.

Two hundred sixteen abstracts were selected for presentation at the 2024 American College of Medical Toxicology (ACMT) Annual Scientific Meeting on April 12-14, 2024, in Washington, DC. The quality and breadth of toxicology scholarship continues to grow as our field expands. The complete 2024 ASM abstract book in the April issue of JMT includes original research studies from around the world and the ToxIC Investigators Consortium, clinically significant case reports describing toxicologic phenomena, and selected encore research presentations from other scientific meetings.

Concurrent Alcohol and Opioid Intoxication in Emergency Department Patients Leads to Greater Resource Utilization.

Background: Concurrent alcohol intoxication can complicate emergency department (ED) presentations for opioid-related adverse events. We sought to determine if there was a difference in resource utilization among patients who presented to the ED with concurrent opioid and alcohol intoxication compared to opioid intoxication alone. Methods: Using linked state-wide databases from the Maryland Healthcare Cost and Utilization Project (HCUP), we identified patients with a diagnosis of opioid intoxication treated in the ED from 2016 to 2018. We measured healthcare utilization for each patient in the ED settings for one year after the initial ED visit and estimated direct costs. We performed logistic regression comparing patients presented with co-intoxication to those without. Results: Of 12,295 patients who presented to the ED for opioid intoxication during the study period, 703 (5.7%) had concurrent alcohol intoxication. Patients with co-intoxication had more recurrent ED visits (340 vs 247.4 per 1000 patients, p < 0.05), higher index ED visit admission rates (26.9% vs 19.4%, p < 0.001), but similar overall costs ($3736 vs $2861, p < 0.05) at one year. Co-intoxication was associated with suicidal ideation (OR = 1.58, 95% CI 1.51-1.65), high zip code income (OR = 1.16, 95% CI 1.12-1.21), and higher rates of intoxication with all classes of drugs analyzed (p < 0.001). Conclusion: Our study demonstrated that mental health disorders, socioeconomic status, and increased ED utilization are associated with co-intoxication of opioids and alcohol presenting to the ED. Further research is needed to elucidate factors responsible for the increased resource use in this population.

Beyond the Four Walls: The American College of Emergency Physicians 2022 New Practice Models Task Force Report.

Emergency physicians are highly trained to deliver acute unscheduled care. The emergency physician core skillset gained during emergency medicine residency can be applied to many other roles that benefit patients and extend and diversify emergency physician careers. In 2022, the American College of Emergency Physicians (ACEP) convened the New Practice Models Task Force to describe new care models and emergency physician opportunities outside the 4 walls of the emergency department. The Task Force consisted of 21 emergency physicians with broad experience and 2 ACEP staff. Fifty-nine emergency physician roles were identified (21 established clinical roles, 16 emerging clinical roles, 9 established nonclinical roles, and 13 emerging nonclinical roles). A strength-weakness-opportunity-threat (SWOT) analysis was performed for each role. Using the analysis, the Task Force made recommendations for guiding ACEP internal actions, advocacy, education, and research opportunities. Emphasis was placed on urgent care, rural medicine, telehealth/virtual care, mobile integrated health care, home-based services, emergency psychiatry, pain medicine, addiction medicine, and palliative care as roles with high or rising demand that draw on the emergency physician skillset. Advocacy recommendations focused on removing state and federal regulatory and legislative barriers to the expansion of new and emerging roles. Educational recommendations focused on aggregating available resources, developing a centralized resource for career guidance, and new educational content for emerging roles. The Task Force also recommended promoting research on potential advantages (eg, improved outcomes, lower cost) of emergency physicians in certain roles and new care models (eg, emergency physician remote supervision in rural settings).

Opioid and Benzodiazepine Co-Prescribing Trends from the Emergency Department from 2012 to 2019: A National Analysis.

BACKGROUND: In 2016, the U.S. Food and Drug Administration (FDA) issued its strongest safety warning ("Black Box Warning") for concomitant use of prescription opioids and benzodiazepines due to overdose deaths. OBJECTIVE: Our objective was to look at trends of opioid and benzodiazepine co-prescribing in the emergency department (ED) using national data, because recent data are sparse. METHODS: This is a retrospective review of data collected by the National Hospital Ambulatory Medical Care Survey between 2012 and 2019. Our primary outcome was to determine whether there was a trend in ED visits when opioids and benzodiazepines were co-prescribed at discharge. We also compared the rate of visits when co-prescribing occurred before (2012-2015) and after (2017-2019) the 2016 FDA warning. We identified commonly co-prescribed benzodiazepines and opioids, and the rate of naloxone co-prescribing. We used descriptive statistics and bivariate tests to describe data. RESULTS: Between 2012 and 2019, there were 4,489,613 ED visits (0.41% of ED visits) when benzodiazepines and opioids were co-prescribed. There was no trend in the rate of co-prescribing overall, but a decrease in visits after the 2016 FDA Black Box Warning (2012-2015: mean 0.49%; 2017-2019: mean 0.29%; p < 0.0001). There were 7980 ED visits (0.18%) when naloxone was co-prescribed for these visits within this time frame and an increase over time (p < 0.001). CONCLUSIONS: Our study found that between 2012 and 2019, there was no overall reduction in co-prescribing of opioids and benzodiazepines across EDs nationwide, but a decrease after the 2016 Black Box Warning.

American College of Medical Toxicology and the American Academy of Clinical Toxicology position statement: nalmefene should not replace naloxone as the primary opioid antidote at this time.

BACKGROUND: Nalmefene is a potent opioid antagonist that has recently been reintroduced in the United States to treat known or suspected opioid overdose. NALMEFENE CLINICAL TRIAL DATA: The injection formulation, which had been withdrawn in 2008, was reintroduced in 2022, and in 2023 the United States Food and Drug Administration approved a new intranasal formulation of nalmefene. Because nalmefene had been previously approved for use in 1995 via injection, the new intranasal formulation did not require new clinical data as it was approved under an Abbreviated New Drug Application. Inherent to this abbreviated approval process, intranasal nalmefene was not studied in patients currently suffering opioid overdose. NALOXONE AND NALMEFENE: Nalmefene also has unique characteristics compared with naloxone, the current standard opioid antidote. Nalmefene has a higher affinity for opioid receptors and a longer duration of action than naloxone. Comparative effectiveness data regarding naloxone and nalmefene are sparse, and it is unclear if the inherent properties of nalmefene are beneficial in opioid overdose. We have decades of experience using naloxone safely and effectively as the primary opioid antidote, even in cases of fentanyl and fentanyl analog overdoses. There is, however, evidence to suggest nalmefene may result in more prolonged and severe opioid withdrawal than naloxone, which could be harmful to patients. POSITION: As nalmefene is untested in the current clinical environment of synthetic opioid overdoses and has the potential to cause harm via prolonged withdrawal, it is the opinion of the American College of Medical Toxicology and the American Academy of Clinical Toxicology that nalmefene should not replace naloxone as the primary opioid antidote at this time. RECOMMENDATIONS: We recommend additional clinical studies of nalmefene, administered via all approved routes, be conducted in a comparative fashion with naloxone, and that safety and effectiveness outcomes be evaluated before nalmefene is recommended as a primary opioid antidote.

Emergency department approach to monkeypox.

BACKGROUND: Monkeypox (mpox) is a viral infection that is primarily endemic to countries in Africa, but large outbreaks outside of Africa have been historically rare. In June 2022, mpox began to spread across Europe and North America, causing the World Health Organization (WHO) to declare mpox a public health emergency of international concern. This article aims to review clinical presentation, diagnosis, and prevention and treatment strategies on mpox, providing the basic knowledge for prevention and control for emergency providers. METHODS: We conducted a review of the literature using PubMed and SCOPUS databases from their beginnings to the end of July 2023. The inclusion criteria were studies on adult patients focusing on emerging infections that described an approach to a public health emergency of international concern, systematic reviews, clinical guidelines, and retrospective studies. Studies that were not published in English were excluded. RESULTS: We included 50 studies in this review. The initial symptoms of mpox are non-specific: fever, malaise, myalgias, and sore throat. Rash, a common presentation of mpox, usually occurs 2-4 weeks after the prodrome, but the presence of lymphadenopathy may distinguish mpox from other infections from the Poxviridae family. Life-threatening complications such as pneumonia, sepsis, encephalitis, myocarditis, and death can occur. There are documented co-occurrences of human immunodeficiency virus (HIV) and other sexually transmitted infections that can worsen morbidity. CONCLUSION: The initial presentation of mpox is non-specific. The preferred treatment included tecovirimat in patients with severe illness or at high risk of developing severe disease and vaccination with two doses of JYNNEOS. However, careful history and physical examination can raise the clinicians' suspicion and point toward a prompt diagnosis. There are different modalities to prevent and treat mpox infection.

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.

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.

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.

Efficacy and tolerability of oral morphine versus oxycodone/acetaminophen for analgesia in the emergency department.

OBJECTIVE: Oxycodone/acetaminophen is one of the most commonly prescribed medications for pain management in the emergency department (ED) despite its high abuse liability. Our objective was to determine whether oral immediate-release morphine is as effective and well tolerated as oral oxycodone/acetaminophen for pain relief in stable ED patients. DESIGN: This is a prospective comparative study in which stable adult patients with acute painful conditions who had either oral morphine (15 or 30 mg) or oxycodone/acetaminophen (5/325 mg or 10/650 mg) ordered for them at the discretion of a triage physician were recruited. SETTING: This study took place in an urban, academic ED from 2016 to 2019. PARTICIPANTS: Seventy-three percent of the subjects were between the ages of 18 and 59, 57 percent were female, and 85 percent were African American. Most presented with abdominal, extremity, or back pain. Patient characteristics were similar between treatment groups. INTERVENTIONS: Of the 364 enrolled patients, 182 were given oral morphine and 182 were given oxycodone/acetaminophen at the discretion of the triage provider. They were asked to rate their pain score prior to receiving analgesia and at 60 and 90 minutes after administration. MAIN OUTCOME MEASURES: We examined pain scores, adverse effects, overall satisfaction, willingness to accept the same treatment again, and the need for additional analgesia. RESULTS: There was no difference in satisfaction reported by patients who received morphine versus oxycodone/acetaminophen: 15.9 percent vs 16.5 percent were very satisfied, 31.9 percent vs 26.4 percent were somewhat satisfied, and 23.6 percent vs 22.5 percent were not satisfied, p = 0.56. Secondary outcomes also showed no significant difference: net change in pain score -2 vs -2 at 60 and 90 minutes, p = 0.91 and p = 0.72, respectively; adverse effects 20.9 percent vs 19.2 percent, p = 0.69; need for further analgesia 9.3 percent vs 7.1 percent, p = 0.44; willingness to accept analgesic again 73.1 percent vs 78.6 percent, p = 0.22. CONCLUSIONS: Oral morphine is a feasible alternative to oxycodone/acetaminophen for analgesia in the ED.

Tacrolimus toxicity due to enzyme inhibition from ritonavir.

Tacrolimus is commonly used for immunosuppression in patients following solid organ transplantation. For transplant patients with COVID-19 infection, early treatment is indicated due to the risk of progression to severe disease. However, the first line agent, nirmatrelvir/ritonavir, has multiple drug-drug interactions. We report a case of tacrolimus toxicity in a patient with a history of renal transplant due to enzyme inhibition related to nirmatrelvir/ritonavir. An 85-year-old woman with a history of multiple comorbidities presented to the emergency department (ED) with weakness, increasing confusion, poor oral intake, and inability to walk. She had been recently diagnosed with COVID-19 infection and was prescribed nirmatrelvir/ritonavir due to her underlying comorbidities and immune suppression. In the ED, she was dehydrated and had an acute kidney injury (creatinine 2.1 mg/dL, up from a baseline of 0.8 mg/dL). The tacrolimus concentration on initial labs was 143 ng/mL (5-20 ng/mL) and it continued to rise despite being held, to a peak of 189 ng/mL on hospital day 3. The patient was treated with phenytoin for enzyme induction and the tacrolimus concentration began to fall. She was discharged to a rehabilitation facility after a 17 day hospitalization. ED physicians must be cognizant of drug-drug interactions when prescribing nirmatrelvir/ritonavir and evaluating patients recently treated with the drug to identify toxicity due to these interactions.