Veratrum parviflorum poisoning: identification of steroidal alkaloids in patient blood and breast milk.

INTRODUCTION: The Veratrum genus is composed of plants containing a diverse set of steroidal alkaloids. Veratrum plant material has been utilized for centuries as herbal medicines, however the alkaloids have such a low therapeutic index that they are not used in modern medicine. Here we report an incident of inadvertent ingestion of V. parviflorum by hikers in Georgia that allowed detection, and in several instances identification of alkaloids from the plant, and correlated their presence within patient blood and breast milk specimens. CASE HISTORY: Eight patients, three male and five female, presented in the spring of 2020 and 2021 with symptoms requiring emergent medical attention after ingestion of Veratrum parviflorum. All patients believed the plants to be a local native species of wild leek, Allium tricoccum, locally known as ramps. Plants were identified using photographs as well as fresh and cooked plant material provided by patients, in consultation with botanists at the University of Georgia Herbarium. Written consent was obtained from all patients for collection of blood and breast milk specimens for laboratory identification of Veratrum alkaloids. METHODS: V. parviflorum plant material, and patient serum and breast milk were analyzed by high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-QTOF) to identify steroidal alkaloids. RESULTS: The V. parviflorum extract was confirmed to contain cyclopamine, veratramine, jervine, and muldamine. Two out of the eight patients had detectable concentrations of Veratrum alkaloids. Of the alkaloids identified in the plant, cyclopamine and jervine were detected within patient serum, and cyclopamine and veratramine were observed to be present in breast milk. DISCUSSION: Toxicity resulting from Veratrum steroidal alkaloids has primarily been reported from V. album and V. viride. This is the second report of V. parviflorum poisoning. The present work reports for the first time the presence of muldamine and jervine within V. parviflorum. This work provides the first instance of identification of Veratrum alkaloids in breast milk. Thus, the findings presented herein add to literature record causative agents contributing to the toxicity of V. parviflorum when ingested and potential for secondary poisoning through breastfeeding. CONCLUSION: V. parviflorum toxicity was observed to cause nausea, vomiting, hypotension, bradycardia, abdominal pain, light-headedness, blurred vision, and tingling in the arms. Patients experiencing mild symptoms improved with supportive care, IV fluids, and antiemetics, but hemodynamically unstable patients required atropine and vasopressors. This study demonstrated that more lipophilic Veratrum alkaloids can be passed along in breast milk, which suggests additional precautions may be critical to limit further poisonings.

Two Cases of Serotonin Syndrome After Bupropion Overdose Treated With Cyproheptadine.

BACKGROUND: Bupropion is not known to have direct serotonin agonism or inhibit serotonin reuptake. In spite of this, it has been implicated as a causative agent of serotonin syndrome. We highlight two cases of single-agent bupropion overdose that subsequently met the diagnosis of serotonin syndrome by the Hunter criteria, despite the absence of direct serotonergic agents. CASE 1: A 14-year-old boy intentionally ingested an estimated 30 bupropion 75-mg immediate-release tablets. He presented in status epilepticus, was intubated, and was placed on midazolam and fentanyl infusions. He developed tremor, ankle clonus, and agitation. He was administered cyproheptadine for presumed serotonin syndrome with temporal improvement in his symptoms. CASE 2: A 19-year-old woman intentionally ingested an estimated 53 bupropion 150-mg extended-release tablets. She had a seizure and required sedation and intubation. During her course, she developed hyperthermia, inducible clonus, and hyperreflexia. She was treated with cyproheptadine without temporal improvement of symptoms but improved the following day. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although bupropion is not known to be directly serotonergic, it has been implicated as the single causative agent after overdose. This may be due to an indirect increase in activity of serotonergic cells. In these cases, bupropion overdose resulted in a clinical presentation consistent with serotonin syndrome, with the first having a temporal improvement after treatment with cyproheptadine. Physicians need to be aware of the potential serotonergic activity of bupropion for accurate assessment and treatment of this dangerous condition.

Hospitalizations and Deaths Associated with EVALI.

BACKGROUND: As of January 7, 2020, a total of 2558 hospitalized patients with nonfatal cases and 60 patients with fatal cases of e-cigarette, or vaping, product use-associated lung injury (EVALI) had been reported to the Centers for Disease Control and Prevention (CDC). METHODS: In a national study, we compared the characteristics of patients with fatal cases of EVALI with those of patients with nonfatal cases to improve the ability of clinicians to identify patients at increased risk for death from the condition. Health departments reported cases of EVALI to the CDC and included, when available, data from medical-record abstractions and patient interviews. Analyses included all the patients with fatal or nonfatal cases of EVALI that were reported to the CDC as of January 7, 2020. We also present three case reports of patients who died from EVALI to illustrate the clinical characteristics common among such patients. RESULTS: Most of the patients with fatal or nonfatal cases of EVALI were male (32 of 60 [53%] and 1666 of 2498 [67%], respectively). The proportion of patients with fatal or nonfatal cases was higher among those who were non-Hispanic white (39 of 49 [80%] and 1104 of 1818 [61%], respectively) than among those in other race or ethnic groups. The proportion of patients with fatal cases was higher among those 35 years of age or older (44 of 60 [73%]) than among those younger than 35 years, but the proportion with nonfatal cases was lower among those 35 years of age or older (551 of 2514 [22%]). Among the patients who had an available medical history, a higher proportion of those with fatal cases than those with nonfatal cases had a history of asthma (13 of 57 [23%] vs. 102 of 1297 [8%]), cardiac disease (26 of 55 [47%] vs. 115 of 1169 [10%]), or a mental health condition (32 of 49 [65%] vs. 575 of 1398 [41%]). A total of 26 of 50 patients (52%) with fatal cases had obesity. Half the patients with fatal cases (25 of 54 [46%]) were seen in an outpatient setting before hospitalization or death. CONCLUSIONS: Chronic conditions, including cardiac and respiratory diseases and mental health conditions, were common among hospitalized patients with EVALI.

Single-Agent Bupropion Exposures: Clinical Characteristics and an Atypical Cause of Serotonin Toxicity.

INTRODUCTION: Bupropion is the only Food and Drug Administration-approved synthetic cathinone. It increases the release of norepinephrine in the locus coeruleus and dorsal raphe nucleus, causing an increase in the frequency of serotonergic neuron firing. The diagnosis of serotonin toxicity (ST) from bupropion poisoning is controversial due to the lack of direct serotonergic activity. Nonetheless, there is one documented report of ST after single-agent bupropion overdose and multiple reports describing polypharmacy overdoses where bupropion may have contributed to ST. METHODS: This is a retrospective analysis of data collected by the Toxicology Investigators Consortium (ToxIC), a prospective multi-center toxico-surveillance and research network registry, from 2014 to 2017. Cases were identified if ST was a clinical effect and bupropion was the single agent listed. Data is presented descriptively. RESULTS: Of the 266 recorded single bupropion overdoses, the most common symptoms were seizures (47.1%), tachycardia (greater than 140 bpm) (33.9%), agitation (31.7%), toxic psychosis (20.4%), and myoclonus/tremor/hyperreflexia (19%). Benzodiazepines were the most common therapy (69.2%). Thirteen patients (5.9%) were diagnosed with ST by a medical toxicologist. CONCLUSION: Bupropion overdose is primarily associated with seizures, tachycardia, and agitation; bupropion may be an atypical cause of serotonin toxicity.

Update: Interim Guidance for Health Care Providers for Managing Patients with Suspected E-cigarette, or Vaping, Product Use-Associated Lung Injury - United States, November 2019.

CDC, the Food and Drug Administration (FDA), state and local health departments, and public health and clinical stakeholders are investigating a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) (1). CDC has published recommendations for health care providers regarding EVALI (2-4). Recently, researchers from Utah and New York published proposed diagnosis and treatment algorithms for EVALI (5,6). EVALI remains a diagnosis of exclusion because, at present, no specific test or marker exists for its diagnosis, and evaluation should be guided by clinical judgment. Because patients with EVALI can experience symptoms similar to those associated with influenza or other respiratory infections (e.g., fever, cough, headache, myalgias, or fatigue), it might be difficult to differentiate EVALI from influenza or community-acquired pneumonia on initial assessment; EVALI might also co-occur with respiratory infections. This report summarizes recommendations for health care providers managing patients with suspected or known EVALI when respiratory infections such as influenza are more prevalent in the community than they have been in recent months (7). Recommendations include 1) asking patients with respiratory, gastrointestinal, or constitutional symptoms about the use of e-cigarette, or vaping, products; 2) evaluating those suspected to have EVALI with pulse oximetry and obtaining chest imaging, as clinically indicated; 3) considering outpatient management for clinically stable EVALI patients who meet certain criteria; 4) testing patients for influenza, particularly during influenza season, and administering antimicrobials, including antivirals, in accordance with established guidelines; 5) using caution when considering prescribing corticosteroids for outpatients, because this treatment modality has not been well studied among outpatients, and corticosteroids could worsen respiratory infections; 6) recommending evidence-based treatment strategies, including behavioral counseling, to help patients discontinue using e-cigarette, or vaping, products; and 7) emphasizing the importance of annual influenza vaccination for all persons aged ≥6 months, including patients who use e-cigarette, or vaping products.

Update: Interim Guidance for Health Care Providers Evaluating and Caring for Patients with Suspected E-cigarette, or Vaping, Product Use Associated Lung Injury - United States, October 2019.

CDC, the Food and Drug Administration (FDA), state and local health departments, and public health and clinical partners are investigating a multistate outbreak of lung injury associated with the use of electronic cigarette (e-cigarette), or vaping, products. In late August, CDC released recommendations for health care providers regarding e-cigarette, or vaping, product use associated lung injury (EVALI) based on limited data from the first reported cases (1,2). This report summarizes national surveillance data describing clinical features of more recently reported cases and interim recommendations based on these data for U.S. health care providers caring for patients with suspected or known EVALI. It provides interim guidance for 1) initial clinical evaluation; 2) suggested criteria for hospital admission and treatment; 3) patient follow-up; 4) special considerations for groups at high risk; and 5) clinical and public health recommendations. Health care providers evaluating patients suspected to have EVALI should ask about the use of e-cigarette, or vaping, products in a nonjudgmental and thorough manner. Patients suspected to have EVALI should have a chest radiograph (CXR), and hospital admission is recommended for patients who have decreased blood oxygen (O2) saturation (<95%) on room air or who are in respiratory distress. Health care providers should consider empiric use of a combination of antibiotics, antivirals, or steroids based upon clinical context. Evidence-based tobacco product cessation strategies, including behavioral counseling, are recommended to help patients discontinue use of e-cigarette, or vaping, products. To reduce the risk of recurrence, patients who have been treated for EVALI should not use e-cigarette, or vaping, products. CDC recommends that persons should not use e-cigarette, or vaping, products that contain tetrahydrocannabinol (THC). At present, CDC recommends persons consider refraining from using e-cigarette, or vaping, products that contain nicotine. Irrespective of the ongoing investigation, e-cigarette, or vaping, products should never be used by youths, young adults, or women who are pregnant. Persons who do not currently use tobacco products should not start using e-cigarette, or vaping, products.

Severe Pulmonary Disease Associated with Electronic-Cigarette-Product Use - Interim Guidance.

On September 6, 2019, this report was posted as an MMWR Early Release on the MMWR website (https://www.cdc.gov/mmwr). As of August 27, 2019, 215 possible cases of severe pulmonary disease associated with the use of electronic cigarette (e-cigarette) products (e.g., devices, liquids, refill pods, and cartridges) had been reported to CDC by 25 state health departments. E-cigarettes are devices that produce an aerosol by heating a liquid containing various chemicals, including nicotine, flavorings, and other additives (e.g., propellants, solvents, and oils). Users inhale the aerosol, including any additives, into their lungs. Aerosols produced by e-cigarettes can contain harmful or potentially harmful substances, including heavy metals such as lead, volatile organic compounds, ultrafine particles, cancer-causing chemicals, or other agents such as chemicals used for cleaning the device (1). E-cigarettes also can be used to deliver tetrahydrocannabinol (THC), the principal psychoactive component of cannabis, or other drugs; for example, "dabbing" involves superheating substances that contain high concentrations of THC and other plant compounds (e.g., cannabidiol) with the intent of inhaling the aerosol. E-cigarette users could potentially add other substances to the devices. This report summarizes available information and provides interim case definitions and guidance for reporting possible cases of severe pulmonary disease. The guidance in this report reflects data available as of September 6, 2019; guidance will be updated as additional information becomes available.

Clinical and Demographic Parameters of Patients Treated Using a Sepsis Protocol.

PURPOSE: The purpose of this study was to investigate potential differences by sex in the demographic and clinical characteristics of patients treated utilizing a sepsis electronic bundle order set. Risk factors for in-hospital mortality were also assessed. METHODS: Data on patients in whom the sepsis order set was initiated in the emergency department over a 16-month period were entered into the hospital database. Data were analyzed for differences by sex in demographic and clinical factors, treatment modalities, and in-hospital mortality. The Bonferroni correction was applied to account for multiple comparisons; α was set at 0.006 for sex differences. FINDINGS: A total of 2204 patients were included. Male and female cohorts were similar with regard to a variety of demographic and clinical factors, including age, Emergency Severity Index (ESI) levels 1 and 2, time to disposition, appropriateness of antibiotics, and total fluids given by weight. The ESI is an assessment score ranging from 1 to 5 (1 is emergent). There were modest differences in the source of infection (genitourinary was 4% more common in women; P = 0.03) and mode of arrival (men were 4% more likely to arrive by ambulance; P = 0.03). These differences did not achieve our predefined α of 0.006 when the Bonferroni correction was applied. Factors associated with in-hospital mortality were advanced age, arrival by ambulance, and an ESI level of 1 or 2 (all, P < 0.01). IMPLICATIONS: Women were more likely to have a genitourinary cause of sepsis and less likely to arrive by ambulance. Risk factors of in-hospital mortality were older age, arrival by ambulance, and an ESI level of 1 or 2, but not sex.

A Case Report of Massive Acetaminophen Poisoning Treated with a Novel "Triple Therapy": N-Acetylcysteine, 4-Methylpyrazole, and Hemodialysis.

Massive acetaminophen (N-acetyl-p-aminophenol; APAP) ingestion is characterized by a rapid onset of mitochondrial dysfunction, including metabolic acidosis, lactemia, and altered mental status without hepatotoxicity which may not respond to the standard doses of N-acetylcysteine (NAC). A 64-year-old woman without medical history presented comatose after an ingestion of 208 tablets of Tylenol PM™ (APAP 500 mg and diphenhydramine 25 mg). The initial APAP concentration measured 1,017 µg/mL (therapeutic range 10-30 µg/mL), and elevated anion gap metabolic acidosis, lactemia, and 5-oxoprolinemia were detected. High-dose intravenous (IV) NAC, 4-methylpyrazole (4-MP), and hemodialysis (HD) were initiated. She was transferred to a liver transplant center and continued both NAC and HD therapies until complete resolution of metabolic acidosis and coma without developing hepatitis. She was discharged without sequelae. This is the fourth highest APAP concentration recorded in a surviving patient. Moreover, this is the first report of a novel "triple therapy" using NAC, 4-MP, and HD in the setting of massive APAP ingestion that presents with coma, elevated anion gap metabolic acidosis, and lactemia. Emergency physicians should recognize these critically ill patients and consider high-dose NAC, 4-MP, and HD to be initiated in the emergency department (ED).

Perception and Practice Among Emergency Medicine Health Care Providers Regarding Discharging Patients After Opioid Administration.

PURPOSE: This study aimed to determine the current attitudes, perceptions, and practices of emergency medicine providers and nurses (RNs) regarding the discharge of adult patients from the emergency department (ED) after administration of opioid analgesics. METHODS: A cross-sectional survey was administered at 3 hospital sites with a combined annual ED census of >180,000 visits per year. All 59 attending emergency physicians (EPs), 233 RNs, and 23 advanced practice clinicians (APCs) who worked at these sites were eligible to participate. FINDINGS: Thirty-five EPs (59.3%), 88 RNs (37.8%), and 14 APCs (60.9%) completed the survey for an overall response rate of 51.75%. Most respondents were female (95 [69.9%]). The factor ranked most important to consider when discharging a patient from the ED after administration of opioids was the patient's functional status and vital signs (median, 2.00; interquartile range, 2.00-3.50). More RNs (84 [96.6%]) than EPs (29 [82.9%]) reported that developing an ED policy or guideline for safe discharge after administration of opioids is important to clinical practice (P = 0.02). Only 8 physicians (23.5%) reported that they did not prescribe intramuscular morphine, and 15 (42.9%) reported that they did not prescribe intramuscular hydromorphone. EPs (7 [20.0%]) and RNs (3 [3.4%]) differed in regard to whether they were aware if any patients to whom they administered an opioid had experienced an adverse drug-related event (P = 0.01). Most EPs (24 [68.6%]) and RNs (54 [61.4%]) believed that the decision for patient discharge should be left to both the emergency medicine provider and the RN. IMPLICATIONS: Most study participants believed that developing a policy or guideline for safe discharge after administration opioids in the ED is important to clinical practice. Only a few physicians reported that they did not prescribe intramuscular hydromorphone or morphine. Most participants believed the discharge decision after administration of opioids in the ED should be primarily determined by both the emergency medicine provider and the RN.