Gillian A. Beauchamp

Successful Treatment of a Massive Metoprolol Overdose Using Intravenous Lipid Emulsion and Hyperinsulinemia/Euglycemia Therapy

Adrenergic β‐antagonists, commonly known as β‐blockers, are prescribed for many indications including hypertension, heart failure, arrhythmias, and migraines. Metoprolol is a moderately lipophilic β‐blocker that in overdose causes direct myocardial depression leading to bradycardia, hypotension, and the potential for cardiovascular collapse. We describe the case of a 59‐year‐old man who intentionally ingested ~7.5 g of metoprolol tartrate. Initial treatment of bradycardia and hypotension included glucagon, atropine, dopamine, and norepinephrine. Despite these treatment modalities, the patient developed cardiac arrest. Intravenous lipid emulsion (ILE) and hyperinsulinemia/euglycemia (HIE) therapies were initiated during advanced cardiac life support and were immediately followed by return of spontaneous circulation. Further treatment included gastric lavage, activated charcoal, continued vasopressor therapy, and a repeat bolus of ILE. The patient was weaned off vasoactive infusions and was extubated within 24 hours. HIE therapy was continued for 36 hours after metoprolol ingestion. A urine β‐blocker panel using mass spectrometry revealed a metoprolol concentration of 120 ng/ml and the absence of other β‐blocking agents. To date, no clear treatment guidelines are available for β‐blocker overdose, and the response to toxic concentrations is highly variable. In this case of a life‐threatening single‐agent metoprolol overdose, the patient was successfully treated with HIE and ILE therapy. Due to the increasing frequency with which ILE and HIE are being used for the treatment of β‐blocker overdose, clinicians should be aware of their dosing strategies and indications.

Quantitative analysis of powdered caffeine products purchased from the Internet using liquid chromatography–quadrupole time-of-flight mass spectrometry

ABSTRACT Context: Powdered caffeine is sold on the Internet as a supplement. Severe toxicity and fatalities have been reported with use, but it is unclear if this toxicity was due to excessive dosing, mislabeled products, or adulterant stimulants. Our objective was to analyze the contents of commercially available powdered caffeine products in order to assess product purity and presence of additional ingredients, contaminants, or adulterants which may contribute to toxicity. Methods: A sample of nine powdered caffeine products was purchased from the Internet. Two sample replicates of each caffeine product were analyzed. Liquid chromatography–quadrupole time-of-flight mass spectrometry (LC-QTOF/MS) was used to identify and quantify substances in the purchased products and purity of the compounds were calculated. Results: Comparison of actual mass versus labeled mass of caffeine demonstrated a mean purity of 88.25% (SD 13.41%) and median purity of 90.1%. The products studied contained 1.6–5.3 g per teaspoon. Labeling on these products had limited instructions regarding how to measure the recommended dose. Conclusions: Powdered caffeine products that are readily available on the Internet contained relatively pure caffeine with no additional detected stimulants. High purity, small serving size, and lack of clear dosing instructions may place users at risk of toxicity.

Adolescent intentional abuse ingestions: overall 10-year trends and regional variation

Objective Adolescent intentional ingestions remain a significant public health problem in the United States with little research to date on the over-the-counter or prescription medicines that adolescents abuse. These data are important for anticipatory guidance by primary care providers, preventive health, and poison center outreach. Methods This was an observational study using the American Association of Poison Control Centers National Poison Data System. The study population consisted of all cases of patients aged 13 to 19 years from 2004 to 2013 with a coding of “intentional abuse.” Results There were 95,695 patient calls that were coded for intentional abuse between 2004 and 2013 for adolescents aged 13 to 19 years. The most common agent reportedly ingested in intentional-abuse cases was antihistamine and/or decongestant with dextromethorphan, and this agent remained the most common throughout the 10-year study period. The next 4 most common agents remained similar across the study period as well and included ethanol, benzodiazepines, dextromethorphan alone, and marijuana. These 5 agents remained the most commonly reported across the study period for all US regions (West, Midwest, South Northeast, and US territories). Conclusions Over a recent 10-year period, common cough preparations remain the most commonly reported intentional abuse ingestion among all years and regions for adolescents.

Toxicological Emergencies in the Resuscitation Area of a Pediatric Emergency Department: A 12-Month Review.

Objective Few studies of children with toxicological emergencies describe those undergoing acute resuscitation, and most describe exposures to single agents. We describe a 12-month sample of patients evaluated in the resuscitation area of a pediatric emergency department (ED) for a toxicological emergency. Methods We conducted a retrospective chart review of patients in a high-volume, academic pediatric ED. We identified patients evaluated in the ED resuscitation area for toxicological exposure and conducted structured chart reviews to collect relevant data. For all variables of interest, we calculated standard descriptive statistics. Results Of 2999 patients evaluated in the resuscitation area through 12 months (March 2009 to April 2010), we identified 80 (2.7%) whose primary ED diagnosis was toxicological. The mean age was 11.4 years. Eighty-six percent of patients were triaged to the resuscitation area for significantly altered mental status. The most frequent single exposures were ethanol (25%), clonidine (10%), and acetaminophen (5%). At least 1 laboratory test was performed for almost all patients (97%). Interventions performed in the resuscitation area included intravenous access placement (97%), activated charcoal (20%), naloxone (19%), and endotracheal intubation (12%). Eighty-two percent of patients were admitted to the hospital; 37% to the intensive care unit. No patients studied in this sample died and most received only supportive care. Conclusions In a high-volume pediatric ED, toxicological emergencies requiring acute resuscitation were rare. Ethanol and clonidine were the most frequent single exposures. Most patients received diagnostic testing and were admitted. Further studies are needed to describe regional differences in pediatric toxicological emergencies.

Delayed Salicylate Toxicity in a 17-Year-Old Girl With Initially Undetectable Salicylate Concentration 3.9 Hours After Ingestion

AbstractWe report the case of a 17-year-old girl with a 126-mg/kg nonenteric coated aspirin ingestion with nontoxic salicylate concentrations at 1.5 and 3.9 hours postingestion, who developed tinnitus and vomiting an estimated 8 hours postingestion, and who was subsequently found to have a toxic salicylate concentration at 22.7 hours postingestion. This case, as well as previous cases of delayed aspirin therapy, may prompt providers to consider educating patients and their care providers regarding the need to return for further testing if symptoms, such as vomiting or tinnitus, develop after an aspirin ingestion.

Making Surveys Count: Enhancing the Rigor of Survey-Based Research in Medical Toxicology

Survey-based studies in medicine gather important information on an individual or institutional level about demographics, practice patterns, knowledge, experience, attitudes, and behaviors that may otherwise be difficult to observe [1–3]. The often cited National Survey on Drug use and Health (NSDUH), which is sponsored by the Substance Abuse and Mental Health Services Administration (SAMHSA) provides national data on substance abuse in the United States by surveying a random selection of households based on address [4]. The National Institute on Drug Abuse (NIDA) has been conducting the annual ‘Monitoring the Future’ survey of drug use and attitudes among 8th, 10th, and 12th graders since 1975—an effort that continues to shape research, education, and prevention in substance abuse [5]. Surveys may be used as a research strategy in both quantitative and qualitative studies and may provide initial data for hypothesis testing or to inform subsequent study design [2]. A 2013 survey of the New England Journal of Medicine’s physician readership found that 78 % of respondents supported the use of medical marijuana in certain circumstances, sparking debate in the medical community, and revealing the urgent need for further research in this area [6]. Advantages of survey-based studies include obtaining data within a short time frame, relatively low cost, and results based on ‘realworld’ observations [2]. Disadvantages include the challenge of obtaining an adequate response rate, the possibility of data skewing due to non-responders, and difficulty determining the significance of data if an inadequate survey tool or inappropriate survey administration is used [2]. As the discipline of medical toxicology matures and strives to promote excellence in research, toxicologists should aspire to adhere to rigorous methodology in the design, implementation, and reporting of survey-based data. In order to translate the time and effort spent designing a survey into a substantive publication, authors should consider using study design guidelines available through publishers, academic institutions, and the research literature. The publication of high-quality survey studies has potential to shape all aspects of medical toxicology, in as much as such studies are accurate, generalizable, timely, and balance inherent methodological limitations with thoughtful study design. Important steps in designing a survey-based study include formulating a research question and determining if a survey is the best tool to address the construct of interest [7]. A literature review will help to determine if a previously validated survey tool exists [3]. When a survey is the best tool to answer a specific research question, the chosen survey design and approaches to administration should address both reliability and validity to ensure the study is conducted effectively and appropriately [8, 9]. Reliability is the extent to which both the survey instrument, and administration is reproducible [3]. Validity is the extent to which the survey measures the hypothesized concept [1, 3]. Factors that affect reliability and validity include ambiguous survey questions; the use of cognitively burdensome and error-prone verbal answer scales; inadequate survey response options; survey results that do not address the research question; inadequate response rate; failure to adequately characterize non-responders; and a study * Gillian A. Beauchamp beauchamp.gillian@gmail.com

The Toxicologist’s Role in Community Outreach: Engaging Fellows in Education and Advocacy Efforts

In 1953, the first poison control center in the U.S. was formally recognized, and subsequently became a focal point for the efforts of physicians spearheading public education and prevention efforts surrounding the dangers of accidental poisonings in children [1–3].While our poison control centers (PCC) and many of our senior colleagues continue to provide community service through advocacy and educational outreach, many fellowships focus primarily on the management of poisoning emergencies and education of healthcare providers [4]. Care of the poisoned patient is at the heart of what we do as toxicologists, but poisoning prevention advocacy and community education are truly the foundation of what we do. By identifying opportunities for advocacy and community outreach amenable to fellow participation, we can provide fellows with more experiences and a broader perspective of what it means to be a toxicologist. As we explore ways to engage toxicology trainees in education and outreach efforts, we should examine recent and ongoing poisoning prevention advocacy efforts. An inspiring ACMT Ellenhorn Lecture BFrom Bedside to Advocacy,^ delivered at the 2015 North American Congress of Clinical Toxicology (NACCT) by Dr. Fred Henretig, outlined the journey from a single case of pediatric laundry pod exposure managed at the bedside to the resultant national promotion of public education and advocacy of poisoning prevention efforts [5]. Dr. Lewis Goldfrank’s recent presentation on BThe Importance of Toxicologic Research in Global Health^ at NACCT was equally motivating, calling for a commitment to global health efforts and advocating for prevention by generating and sharing of knowledge while engaging in respectful partnerships with national and international organizations [6]. Fellows need to consider that improving public health lies at the root of toxicology, and participating in education and outreach locally and nationally during training is a key first step in engaging in this commitment globally. Poison control centers have traditionally been the primary exposure fellows have to community outreach and poisoning prevention advocacy. Toxicology-trained educators at PCCs provide the public with relevant toxicology information based on toxico-surveillance of the communities they serve [7, 8]. They serve a large and diverse audience including medical personnel, individuals concerned about potential toxicological exposures, policy makers, and news media professionals. Examples of PCC interactions with this community which could be undertaken by fellows include volunteering at safety fairs, developing protocols for local emergency medical services (EMS) agencies, collaborating with local health agencies during outbreaks, and providing education on emerging exposures at training events for public service professionals, such as fire and EMS providers. Medical directors and PCC directors serve as experts in developing content for PCC websites, create educational campaigns based on epidemiological trends, participate in news media interviews, and present both direct and indirect education for the community. Many of these directors also serve on regional and state committees, where they lobby the legislature for continued PCC funding or advocate for legislation supporting poisoning prevention. Most PCCs welcome fellow collaboration and provide mentorship for interested fellows in any of these facets of community education. * G. A. Beauchamp beauchamp.gillian@gmail.com

Administration of CroFab Antivenom by a Helicopter Emergency Medical Service Team

The case presented here highlights an unconventional use of a helicopter emergency medical service (HEMS) to provide a specialized medication to a critically ill patient when definitive transport was delayed. A 39-year-old man presented to a rural hospital 1 hour after sustaining a copperhead envenomation. He developed severe symptoms and was intubated. Arrangements were made for transfer to a tertiary referral center by HEMS, but because of incoming weather conditions, the team would not be able to make the return flight safely. The decision was made for the HEMS team to fly antivenom to the patient, administer the medication, and then transport the patient by ground to the tertiary medical center. This plan was executed, and the patient was safely transported to the accepting facility. Antivenom is most effective when administered early because this will halt the progression of edema and may reverse the systemic effects of envenomation. In this case, HEMS transport of antivenom to the patient with severe toxicity prevented a delay to administration and likely improved the patients outcome. Although the traditional role of HEMS is to provide rapid transport to critically ill patients, HEMS teams can also function to deliver specialized medications to remote settings.

Relating calls to US poison centers for potential exposures to medications to Centers for Disease Control and Prevention reporting of influenza-like illness.

Abstract Context: The Centers for Disease Control (CDC) monitors influenza like illness (ILI) and the National Poison Data System (NPDS) warehouses call data uploaded by US poison centers regarding reported exposures to medication. Objective: We examined the relationship between calls to poison centers regarding reported exposures to medications commonly used to treat ILI and weekly reports of ILI. Materials and Methods: The CDC reports ILI, by age group, for each of 10 Health and Human Services (HHS) regions. We examined NPDS summary data from calls reported to poison centers regarding reported exposures to acetaminophen, cough/cold medications, and promethazine, for the same weeks, age groups, and HHS regions for influenza seasons 2000–2013. ILI and NPDS exposures were examined using graphical plots, descriptive statistics, stepwise regression analysis, and Geographic Information Systems (GIS). Results: About 5,101,841 influenza-like illness cases were reported to the CDC, and 2,122,940 calls regarding reported exposures to medications commonly used to treat ILI, were reported by poison centers to the NPDS over the 13 flu seasons. Analysis of stepwise models of the linear untransformed data involving 24 NPDS data groups and for 60 ILI measures, over the 13 influenza seasons, demonstrated that reported exposures to medications used to treat ILI correlated with reported cases of ILI with a median R2 = 0.489 (min R2 = 0.248, max R2 = 0.717), with mean ± SD of R2 = 0.494 ± 0.121. Median number of parameters used (degrees of freedom – 1) was 7. Conclusions: NPDS data regarding poison center calls for selected ILI medication exposures were highly correlated with CDC ILI data. Since NPDS data are available in real time, it provides complimentary ILI monitoring. This approach may provide public health value in predicting other illnesses which are not currently as thoroughly monitored.

The Toxicologist as Educator: Addressing Pain Management in the Midst of an Opioid Epidemic

We callitthe Bmonthly rant^ at theOregonand AlaskaPoison Center: a rotating student or resident presents a case of an opioid poisoning and a well-prepared overview of the toxicokinetics and toxicodynamics of opioids in overdose. The eyes of the fellows and attendings meet briefly, and the moment is perfect for an in-depth discussion about the complexities of opioid prescribing, pain management, and pitfalls of opioid therapy. What ensues is a carefully designed discussion surrounding several key components of appropriate pain management and iatrogenic addiction. With an increasing focus on the opioid epidemic and prevention of addiction, medical educators are actively working to design pain management curricula. It is worth highlighting that many toxicologists already incorporate this education for rotators on the toxicology service and that toxicologists are a valuable resource for medical educators involved in the re-designing of medical curricula. The toxicology rotation seems an ideal place to formally educate trainees to manage pain while attenuating diversion, adverse effects, polypharmacy, and iatrogenic addiction. Whether students and residents spend a day, a week, or a month on the toxicology service, educators can use this opportunity to introduce new approaches toward opioid use in pain management, thus laying the groundwork to reduce morbidity and mortality from opioids. Participants in the discussions on our service typically include third or fourth year medical students, pharmacy students, and emergency medicine residents on their toxicology rotation, who will go on to treat patients with acute and chronic painful conditions in all fields of medicine. Even early in training, students and residents make astute observations about the challenges and pitfalls surrounding the management of acute and chronic