Anne-Michelle Ruha

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Scholarly Contributions

Chapters

• Ruha, A. (2017). Antivenom: Snake (Native Venomous (Crotaline and Elapid)). In Goldfrank's Toxicologic Emergencies.
• Ruha, A. (2017). Native Venomous Snakes and Lizards. In Goldfrank's Toxicologic Emergencies.
• Ruha, A. (2017). North American Scorpion Envenomations. In Toxinology.
• Ruha, A. (2017). Spider Bites and Scorpion Stings. In Conn's Current Therapy 2017. Elsevier.
• Ruha, A. (2017). North American Scorpion Envenomations. In Critical Care Toxicology. doi:10.1007/978-3-319-20790-2_83-1
• Ruha, A. (2017). Rattlesnakes and Other North American Crotalids. In Critical Care Toxicology. doi:10.1007/978-3-319-20790-2_103-1

Journals/Publications

• Greene, S., Ruha, A. M., Campleman, S., Brent, J., Wax, P., & , T. S. (2020). Epidemiology, Clinical Features, and Management of Texas Coral Snake (Micrurus tener) Envenomations Reported to the North American Snakebite Registry. Journal of medical toxicology : official journal of the American College of Medical Toxicology.
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  Few of the 5000-8000 snakebites reported to poison control centers annually in the USA are attributed to coral snakes. This study describes Texas coral snake envenomations reported to the North American Snakebite Registry.
• Heise, C. W., Cunningham, C., Ruha, A. M., & O'Connor, A. D. (2020). One Bite, Two Patients: Disparate Clinical Courses Following Simultaneous Crotalus oreganus abyssus Envenomation. Wilderness & environmental medicine, 31(3), 354-357.
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  A number of crotaline species have been associated with neurotoxic envenomation in North America. One clinical sign that can occur is myokymia: fine, involuntary, wave-like muscle movements occurring at regular intervals. We report an unusual scenario in which a single snakebite resulted in simultaneous envenomation of 2 patients. Both developed myokymia, with 1 having respiratory compromise. One patient also developed a hypersensitivity reaction to antivenom. Envenomation by the Grand Canyon rattlesnake, Crotalus oreganus abyssus, can produce significant neurotoxicity and resultant respiratory compromise. Antivenom may be helpful but can produce hypersensitivity reactions.
• Levine, M., Ruha, A. M., Wolk, B., Caravati, M., Brent, J., Campleman, S., Wax, P., & , T. N. (2020). When It Comes to Snakebites, Kids Are Little Adults: a Comparison of Adults and Children with Rattlesnake Bites. Journal of medical toxicology : official journal of the American College of Medical Toxicology, 16(4), 444-451.
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  Rattlesnake envenomations are a significant cause of morbidity in the USA. While pediatric rattlesnake envenomations are relatively common, data comparing adult and pediatric patients with rattlesnake envenomations remain limited.
• Offerman, S., Gosen, J., Thomas, S. H., Padilla-Jones, A., Ruha, A. M., & Levine, M. (2020). Bupropion associated seizures following acute overdose: who develops late seizures. Clinical toxicology (Philadelphia, Pa.), 1-7.
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  Bupropion is an antidepressant that is commonly known to cause seizures in overdose. Because of concern for delayed onset of seizures, patients are frequently observed for prolonged periods after overdose. The primary objective is to evaluate the incidence and clinical parameters associated with late seizures following bupropion overdose. This retrospective study of acute bupropion overdose who presented to 26 different hospitals in California and Arizona during an 8 year time period. 437 patients were identified. Tachycardia and altered mental status were common. A total of 122 (27.9%) patients had seizures following their overdose. Only eight patients (1.8%) had a seizure more than 8 h after hospital arrival. None of these patients were asymptomatic on arrival. Among patients with tachycardia on arrival, the odds of having a seizure was 6.7 (95% CI 3.7-10.9); the odds of a seizure more than 8 h after arrival was 5.24 (95% CI 1.2-23.5). Similarly, altered mental status on arrival was significantly associated with the risk of a seizure; OR 3.93 (95% CI 2.21-7.0). Seizures are relatively common, and are associated with antecedent tachycardia or altered mental status.
• Curry, S. C., Padilla-Jones, A., Ruha, A. M., O'Connor, A. D., Kang, A. M., Wilkins, D. G., Jaeschke, H., Wilhelms, K., Gerkin, R. D., & , A. A. (2019). The Relationship Between Circulating Acetaminophen-Protein Adduct Concentrations and Alanine Aminotransferase Activities in Patients With and Without Acetaminophen Overdose and Toxicity. Journal of medical toxicology : official journal of the American College of Medical Toxicology, 15(3), 143-155.
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  Measurement of serum acetaminophen-protein adducts (APAP-CYS) has been suggested to support or refute a diagnosis of acetaminophen (APAP)-induced hepatotoxicity when ingestion histories are unreliable or unavailable and when circulating APAP concentrations are low or undetectable. Non-APAP overdose patients commonly have used APAP products in non-toxic quantities and, thus, will have measurable APAP-CYS concentrations, even when hepatic injury results from other causes, such as ischemic hepatitis. The relationship between alanine aminotransferase (ALT) activity and APAP-CYS concentration might assist in distinguishing between toxic and non-toxic APAP doses in patients suspected of drug overdose.
• Domanski, K., Kleinschmidt, K. C., Greene, S., Ruha, A. M., Bebarta, V. S., Onisko, N., Campleman, S., Brent, J., Wax, P., & , T. N. (2019). Cottonmouth snake bites reported to the ToxIC North American snakebite registry 2013-2017. Clinical toxicology (Philadelphia, Pa.), 1-5.
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  The majority of venomous snake exposures in the United States are due to snakes from the subfamily (pit vipers). There are three types of US pit vipers: rattlesnakes ( and spp.) copperheads (), and cottonmouths () also known as water moccasins. Cottonmouth bites are reported less frequently than other pit viper envenomations, and data on cottonmouth envenomation are limited. Our objective was to describe the epidemiology, clinical manifestations, and management of cottonmouth envenomations using prospective data reported to the Toxicology Investigators Consortium's (ToxIC) North American Snakebite Registry (NASBR) Cottonmouth envenomation cases reported to NASBR for the period from January 1, 2013, through December 31, 2017 were reviewed. Variables collected included patient demographics, bite location, clinical manifestations, and management. Thirty-one cottonmouth envenomations were reported. Most bites occurred in children aged 7-12 (39%). Most bites involved the lower extremity (72%). Intentional interaction with the snake occurred in three cases (10%). Swelling was the most reported clinical effect and occurred in all patients. Gastrointestinal symptoms were reported in 19% of patients, and 19% developed coagulopathy. Antivenom treatment was used in 84% of patients. Nineteen patients (61%) required hospital stays of >24 hours. Our study represents the first systematic prospective data collection on cottonmouth bites. Our data demonstrate that cottonmouth envenomations cause primarily local effects and, occasionally, systemic toxicity. Our study also demonstrates that antivenom is often indicated for these envenomations per published guidelines and recommendations. Cottonmouth envenomations are relatively infrequent. However, they can cause significant local and systemic toxicity. Most cottonmouth envenomations in this series were treated with antivenom and were hospitalized beyond 24 hours.
• Moore, E. C., Porter, L. M., & Ruha, A. M. (2019). Rattlesnake venom-induced recurrent coagulopathy in first trimester pregnant women - Two Cases. Toxicon : official journal of the International Society on Toxinology, 163, 8-11.
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  Delayed or recurrent coagulopathy can occur up to 14 days after North American rattlesnake envenomation in patients that have been treated with Crotalidae Polyvalent Immune Fab (CroFab). There is little data in the literature characterizing the sequelae of North American rattlesnake envenomation in pregnancy and no previously published reports of recurrent coagulopathy in pregnancy. CASE REPORT: We present 2 cases of first trimester pregnant women requiring readmission and retreatment with Crotalidae Polyvalent Immune Fab (CroFab) after developing recurrent/late coagulopathy following North American Rattlesnake Envenomation. Both patients were initially admitted and treated with CroFab following snakebite and discharged home without coagulopathy. One patient developed significant hypofibrinogenemia and subsequent hemorrhage after spontaneous abortion secondary to recurrent venom induced hypofibrinogenemia. DISCUSSION: Pregnant women with recurrent or late coagulopathy may be at higher risk for hemorrhage and spontaneous abortion and require more frequent laboratory monitoring after initial hospitalization and treatment with antivenom. A lower threshold for re-treatment with CroFab may be warranted in patients with fibrinogen less than 100mg/dL even in the setting of a normal platelet count.
• Spyres, M. B., Moore, E. C., Ruha, A. M., & O'Connor, A. D. (2019). Moving Towards Gender Equality in Medical Toxicology. Journal of medical toxicology : official journal of the American College of Medical Toxicology, 15(4), 217-219.
• Chai, P. R., Ruha, A. M., Wong, K. E., Monette, D. L., Spyres, M. B., Lapoint, J., Greller, H., & Mycyk, M. B. (2018). The Virtual Toxicology Journal Club: the Dissemination and Discussion of Noteworthy Manuscripts Using Twitter. Journal of medical toxicology : official journal of the American College of Medical Toxicology, 14(3), 212-217.
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  Twitter-based chat groups (tweetchats) structured as virtual journal clubs have been demonstrated to provide value to learners. In order to promote topics in medical toxicology, we developed the #firesidetox tweetchat as a virtual journal club to discuss and disseminate topics in medical toxicology.
• Kleinschmidt, K., Ruha, A. M., Campleman, S., Brent, J., & Wax, P. (2018). Acute adverse events associated with the administration of Crotalidae polyvalent immune Fab antivenom within the North American Snakebite Registry. Clinical toxicology (Philadelphia, Pa.), 1-6.
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  Crotalidae Polyvalent Immune Fab (Fab Antivenom) is the primary Viperid antivenom used in the United States since 2000. Adverse event data associated with its use are limited. The purpose of this study is to describe the prevalence of acute adverse events associated with the use of Fab antivenom.
• Spyres, M. B., Skolnik, A. B., Moore, E. C., Gerkin, R. D., Padilla-Jones, A., & Ruha, A. M. (2018). Comparison of Antivenom Dosing Strategies for Rattlesnake Envenomation. Critical care medicine, 46(6), e540-e544.
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  This study compares maintenance with clinical- and laboratory-triggered (as-needed [PRN]) antivenom dosing strategies with regard to patient-centered outcomes after rattlesnake envenomation.
• Heise, C. W., Ruha, A. M., Padilla-Jones, A., Truitt Hayek, C., & Gerkin, R. D. (2017). Clinical predictors of tissue necrosis following rattlesnake envenomation. Clinical toxicology (Philadelphia, Pa.), 1-4.
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  Rattlesnake envenomation (RSE) causes edema, hemotoxicity and tissue necrosis. Necrosis may result in permanent disability.
• O'Connor, A. D., Padilla-Jones, A., & Ruha, A. M. (2017). Severe bark scorpion envenomation in adults(). Clinical toxicology (Philadelphia, Pa.), 1-5.
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  The preponderance of medical literature regarding severe bark scorpion envenomation describes pediatric patients; however, the majority (>66%) of annual poison center calls pertain to adults. This retrospective review sought to evaluate the clinical manifestations of adults with severe Centruroides sculpturatus envenomation and determine if significant morbidity occurred.
• Ruha, A. M., Kleinschmidt, K. C., Greene, S., Spyres, M. B., Brent, J., Wax, P., Padilla-Jones, A., Campleman, S., & , T. S. (2017). The Epidemiology, Clinical Course, and Management of Snakebites in the North American Snakebite Registry. Journal of medical toxicology : official journal of the American College of Medical Toxicology.
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  The American College of Medical Toxicology established the North American Snakebite Registry (NASBR), a national database of detailed, prospectively collected information regarding snake envenomation in the United States, in 2013. This report describes the epidemiology, clinical course, and management of snakebites in the NASBR. All cases entered into the NASBR between January 1, 2013 and December 31, 2015 were identified. Descriptive statistics are used to report results. Fourteen sites in 10 states entered 450 snakebites. Native species comprised 99% of cases, almost all of which were pit viper bites. 56.3% were identified as rattlesnakes and 29.4% as copperheads. 69.3% were male and 28.2% were children age 12 and under. Fifty-four percent of bites were on the lower extremity. Twenty-seven percent of patients with lower extremity bites were not wearing shoes. Common tissue findings associated with envenomation were swelling, ecchymosis, and erythema. Systemic effects and hematologic toxicity were more common in rattlesnake than copperhead or cottonmouth envenomations. Crotalidae Polyvalent Immune Fab antivenom was given to 84% of patients. Twelve patients (4.3%) were re-admitted to the hospital after completion of treatment. Eight were re-treated with antivenom. The NASBR gathers detailed data on venomous snakebites across the US. In its initial years, useful information has already been gained. Data regarding footwear will inform public health interventions and education, and information regarding the clinical presentation may help physicians better anticipate effects and manage snakebite. As the number of cases in the NASBR grows, associations between patient-related factors and outcomes may be studied.
• Spyres, M. B., Ruha, A. M., Kleinschmidt, K., Vohra, R., Smith, E., & Padilla-Jones, A. (2017). Epidemiology and clinical outcomes of snakebite in the elderly: a ToxIC database study(). Clinical toxicology (Philadelphia, Pa.), 1-5.
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  Epidemiologic studies of snakebites in the United States report typical victims to be young men. Little is known regarding other demographics including children and the elderly. The objective of this study was to describe the epidemiology and clinical manifestations of snake bite in elderly patients reported to the ToxIC (Toxicology Investigators Consortium) North American Snakebite Registry (NASBR) Methods: This was a multicenter analysis of a prospectively collected cohort of patients with snakebite reported to the ToxIC NASBR between 1 January 2013 and 31 December 2015. Inclusion criterion was age >65. Variables collected included patient demographics, medical comorbidities, medications, date the case was reported to the registry, location of exposure, bite location, snake species, clinical manifestations, outcomes, and management.
• Boyer, L. V., & Ruha, A. (2016). Pitviper Envenomation Guidelines Should Address Choice Between FDA-approved Treatments for Cases at Risk of Late Coagulopathy. Wilderness & environmental medicine, 27(2), 341-2.
• Coorg, V., Levitan, R. D., Gerkin, R. D., Muenzer, J., & Ruha, A. (2016). Clinical Presentation and Outcomes Associated with Different Treatment Modalities for Pediatric Bark Scorpion Envenomation. Journal of medical toxicology : official journal of the American College of Medical Toxicology.
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  Scorpion envenomation is potentially life-threatening and affects children in the Southwestern USA. An FDA-approved antivenom is available, but its high cost has led to use of off-label antivenom dosing or supportive care alone as alternatives to FDA-recommended dosing. This study sought to determine whether treatment approach influences outcomes in envenomated children.
• Farrugia, L. A., Rhyee, S. H., Campleman, S. L., Ruha, A., Weigand, T., Wax, P. M., Brent, J., & , T. I. (2016). The Toxicology Investigators Consortium Case Registry-the 2015 Experience. Journal of medical toxicology : official journal of the American College of Medical Toxicology, 12(3), 224-47.
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  The American College of Medical Toxicology established the Toxicology Investigators Consortium (ToxIC) Case Registry in 2010. The Registry contains all medical toxicology consultations performed at participating sites. The Registry has continued to grow since its inception, and as of December 31, 2015, contains 43,099 cases. This is the sixth annual report of the ToxIC Registry, summarizing the additional 8115 cases entered in 2015. Cases were identified by a query of the Registry for all cases entered between January 1 and December 31, 2015. Specific data reviewed for analysis included demographics (age, race, gender), source of consultation, reason for consultation, agents and agent classes involved in exposures, signs, symptoms, clinical findings, fatalities, and treatment. By the end of 2015, there were 50 active sites, consisting of 101 separate health-care facilities; 51.2 % of cases involved females. Adults between the ages of 19 and 65 made up the majority (64.2 %) of Registry cases. Caucasian race was the most commonly reported (55.6 %); 9.6 % of cases were identified as Hispanic ethnicity. Inpatient and emergency department referrals were by far the most common referral sources (92.9 %). Intentional pharmaceutical exposures remained the most frequent reason for consultation, making up 52.3 % of cases. Of these intentional pharmaceutical exposures, 69 % represented an attempt at self-harm, and 85.6 % of these were a suicide attempt. Nonopioid analgesics, sedative-hypnotics, and antidepressant agents were the most commonly reported agent classes in 2015. Almost one-third of Registry cases involved a diagnosed toxidrome (32.8 %), with a sedative-hypnotic toxidrome being the most frequently described. Significant vital sign abnormalities were recorded in 25.3 % of cases. There were 98 fatalities reported in the Registry (1.2 %). Adverse drug reactions were reported in 4.3 % of cases. Toxicological treatment was given in 65.3 % of cases, with 33.0 % receiving specific antidotal therapy. Exposure characteristics and trends overall were similar to prior years. While treatment interventions were required in the majority of cases, fatalities were rare.
• Lasoff, D. R., Ruha, A., Curry, S. C., Koh, C., & Clark, R. F. (2016). A new F(ab')2 antivenom for the treatment of crotaline envenomation in children. The American journal of emergency medicine, 34(10), 2003-2006.
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  To evaluate the efficacy and safety of a new F(ab')2 antivenom preparation in the treatment of Crotalinae envenomation in children.
• Spyres, M. B., Ruha, A., Seifert, S., Onisko, N., Padilla-Jones, A., & Smith, E. A. (2016). Occupational Snake Bites: a Prospective Case Series of Patients Reported to the ToxIC North American Snakebite Registry. Journal of medical toxicology : official journal of the American College of Medical Toxicology, 12(4), 365-369.
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  In the developing world, occupation has been identified as a risk factor for snake bite. Such an association has not been described in the USA. The objective of this study was to describe the epidemiology and clinical manifestations of occupational snake bite in patients reported to the ToxIC North American Snakebite Registry (NASBR).
• Bush, S. P., Ruha, A., Seifert, S. A., Morgan, D. L., Lewis, B. J., Arnold, T. C., Clark, R. F., Meggs, W. J., Toschlog, E. A., Borron, S. W., Figge, G. R., Sollee, D. R., Shirazi, F. M., Wolk, R., de Chazal, I., Quan, D., García-Ubbelohde, W., Alagón, A., Gerkin, R. D., & Boyer, L. V. (2015). Comparison of F(ab')2 versus Fab antivenom for pit viper envenomation: a prospective, blinded, multicenter, randomized clinical trial. Clinical toxicology (Philadelphia, Pa.), 53(1), 37-45.
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  Crotalidae Polyvalent Immune Fab (Ovine) has been the only antivenom commercially available in the US since 2007 for treatment of Crotalinae envenomation. Late coagulopathy can occur or recur after clearance of Fab antivenom, often after hospital discharge, lasting in some cases more than 2 weeks. There have been serious, even fatal, bleeding complications associated with recurrence phenomena. Frequent follow-up is required, and additional intervention or hospitalization is often necessary. F(ab')2 immunoglobulin derivatives have longer plasma half life than do Fab. We hypothesized that F(ab')2 antivenom would be superior to Fab in the prevention of late coagulopathy following treatment of patients with Crotalinae envenomation.
• Bush, S. P., Ruha, A., Seifert, S. A., Sollee, D. R., & Boyer, L. V. (2015). In reply re: "comparison of F(ab')2 versus Fab antivenom for pit viper envenomation: a prospective, blinded, multicenter, randomized clinical trial". Clinical toxicology (Philadelphia, Pa.), 53(4), 414-5.
• Curry, S. C., Padilla-Jones, A., O'Connor, A. D., Ruha, A., Bikin, D. S., Wilkins, D. G., Rollins, D. E., Slawson, M. H., Gerkin, R. D., & , A. A. (2015). Prolonged Acetaminophen-Protein Adduct Elimination During Renal Failure, Lack of Adduct Removal by Hemodiafiltration, and Urinary Adduct Concentrations After Acetaminophen Overdose. Journal of medical toxicology : official journal of the American College of Medical Toxicology, 11(2), 169-78.
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  Elevated concentrations of serum acetaminophen-protein adducts, measured as protein-derived acetaminophen-cysteine (APAP-CYS), have been used to support a diagnosis of APAP-induced liver injury when histories and APAP levels are unhelpful. Adducts have been reported to undergo first-order elimination, with a terminal half-life of about 1.6 days. We wondered whether renal failure would affect APAP-CYS elimination half-life and whether continuous venovenous hemodiafiltration (CVVHDF), commonly used in liver failure patients, would remove adducts to lower their serum concentrations. Terminal elimination half-lives of serum APAP-CYS were compared between subjects with and without renal failure in a prospective cohort study of 168 adults who had ingested excessive doses of APAP. APAP-CYS concentrations were measured in plasma ultrafiltrate during CVVHDF at times of elevated serum adduct concentrations. Paired samples of urine and serum APAP-CYS concentrations were examined to help understand the potential importance of urinary elimination of serum adducts. APAP-CYS elimination half-life was longer in 15 renal failure subjects than in 28 subjects with normal renal function (41.3 ± 2.2 h versus 26.8 ± 1.1 h [mean ± SEM], respectively, p 
• French, R., Brooks, D., Ruha, A., Shirazi, F., Chase, P., Boesen, K., & Walter, F. (2015). Gila monster (Heloderma suspectum) envenomation: Descriptive analysis of calls to United States Poison Centers with focus on Arizona cases. Clinical toxicology (Philadelphia, Pa.), 53(1), 60-70.
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  The Gila monster (Heloderma suspectum) is a venomous lizard native to the deserts of southwestern United States (US) and northern Mexico. The purpose of this study was to describe human exposures to Gila monsters reported to US poison control centers (PCCs) with a focus on Arizona cases.
• Ruha, A. (2015). Ethical Standards Help to Define the Medical Toxicologist. Journal of medical toxicology : official journal of the American College of Medical Toxicology, 11(4), 383-4.
• Wong, A., Vohra, R., Ruha, A., Koutsogiannis, Z., Graeme, K., Dargan, P. I., Wood, D. M., & Greene, S. L. (2015). The Global Educational Toxicology Uniting Project (GETUP): an Analysis of the First Year of a Novel Toxicology Education Project. Journal of medical toxicology : official journal of the American College of Medical Toxicology, 11(3), 295-300.
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  The international boundaries to medical education are becoming less marked as new technologies such as multiuser videoconferencing are developed and become more accessible to help bridge the communication gaps. The Global Educational Toxicology Uniting Project (GETUP) is aimed at connecting clinicians in countries with established clinical toxicology services to clinicians in countries without clinical toxicologists around the globe. Centers that manage or consult on toxicology cases were registered through the American College of Medical Toxicology website via Survey Monkey®. Data was analyzed retrospectively from February 2014 to January 2015. Google hangouts® was used as the main conferencing software, but some sites preferred the use of Skype®. Registration data included contact details and toxicology background and qualifications. Thirty sites in 19 different countries in Australasia, Europe, Africa, and America were registered. Twenty-eight (93 %) sites were located in a major urban center, one (3.5 %) site in a major rural center and one (3.5 %) a private practice. Expectations of GETUP included sharing toxicology cases and education (30, 100 % of sites), assistance with toxicology management guidelines (2, 7 %), assistance with providing a toxicology teaching curriculum in languages other than English (2, 7 %), and managing toxicology presentations in resource-poor settings, international collaboration, and toxicovigilance (2 sites, 7 %). Twenty-two conferences were performed during the first 12 months with a mean of 3 cases per conference. GETUP has connected countries and clinical units with and without toxicology services and will provide a platform to improve international collaboration in clinical toxicology.
• Bosak, A. R., Ruha, A., & Graeme, K. A. (2014). A case of neurotoxicity following envenomation by the Sidewinder rattlesnake, Crotalus cerastes. Journal of medical toxicology : official journal of the American College of Medical Toxicology, 10(2), 229-31.
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  North American rattlesnake envenomations typically result in local tissue injury and hematologic derangements. Neurotoxicity is uncommon but when present often manifests as fasciculations and paresthesias. Neurotoxicity following Sidewinder (Crotalus cerastes) envenomation has not been previously reported.
• Kopec, K. T., Brent, J., Banner, W., Ruha, A. M., & Leikin, J. B. (2014). Management of cardiac dysrhythmias following hydrocarbon abuse: clinical toxicology teaching case from NACCT acute and intensive care symposium. Clinical toxicology (Philadelphia, Pa.), 52(2), 141-5.
• Levine, M., Curry, S., Ruha, A., & Padilla-Jones, A. (2014). In reply. Annals of emergency medicine, 63(1), 90-1.
• Levine, M., Pizon, A. F., Padilla-Jones, A., & Ruha, A. (2014). Warfarin overdose: a 25-year experience. Journal of medical toxicology : official journal of the American College of Medical Toxicology, 10(2), 156-64.
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  Warfarin, a vitamin K antagonist, is widely used for the prophylaxis and treatment of thromboembolic disease. While guidelines exist for management of a supratherapeutic international normalized ratio following therapeutic warfarin use, these guidelines are not designed for management of the acute warfarin overdose. There is a paucity of literature describing the latter. The primary objective of this manuscript is to characterize the coagulopathy and describe the bleeding events that occur after a warfarin overdose. A secondary goal is to describe the amount of vitamin K administered to patients presenting with warfarin overdoses. A retrospective chart review of patients admitted with an acute warfarin overdose at two tertiary care medical centers in the USA was conducted. Clinical characteristics were abstracted, and bleeding categories (major, minor, trivial) were defined a priori. Twenty-three patients were admitted during the time period; males accounted for 15/23 (62.5 %) subjects. The median (interquartile range (IQR)) age was 43 (32-48.5) years. Seventeen subjects received vitamin K, with a median (IQR) dose of 15 (10-50) mg. The maximal total amount of vitamin K administered to a single patient during the index hospitalization was 110 mg. Three bleeding events occurred; one classified as major, and two as minor. All patients made a full recovery. In this case series of acute warfarin overdose, nearly all patients developed a coagulopathy, and nearly three-quarters of patients received vitamin K. Bleeding events occurred in a minority of patients.
• Levine, M., Ruha, A., Padilla-Jones, A., Gerkin, R., & Thomas, S. H. (2014). Bleeding following rattlesnake envenomation in patients with preenvenomation use of antiplatelet or anticoagulant medications. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine, 21(3), 301-7.
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  Rattlesnake envenomations commonly produce coagulopathy and thrombocytopenia, yet clinically significant bleeding is uncommon. It is unknown if patients who use antiplatelet or anticoagulant medications prior to envenomation are at increased risk for bleeding after envenomation.
• Levine, M., Skolnik, A. B., Ruha, A., Bosak, A., Menke, N., & Pizon, A. F. (2014). Complications following antidotal use of intravenous lipid emulsion therapy. Journal of medical toxicology : official journal of the American College of Medical Toxicology, 10(1), 10-4.
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  The primary objective is to identify and describe the complications associated with the use of intravenous lipid emulsion (ILE) therapy as an antidote for lipophilic drug toxicity. This study is a retrospective chart review of patients treated with ILE at two academic medical centers between 2005 and 2012. Based on previously reported complications, we hypothesized that pancreatitis, ARDS, and lipemia-induced laboratory interference might occur. Clinical definitions of these complications were defined a priori. Subjects treated with ILE who did not develop at least one complication were excluded. A total of nine patients were treated with ILE during the study period, six of whom experienced potential complications as a result of the ILE. Two patients developed pancreatitis, and four patients had lipemia-induced interference of interpretation of laboratory studies, despite ultracentrifugation. Laboratory interference precluded one patient from being an organ donor. Three patients developed ARDS; although temporally associated, a causal relationship between ILE and the development of ARDS cannot be clearly established. As ILE is increasingly used for less severe cases of drug toxicity, clinicians should be aware of potential complications associated with its use. A risk-benefit assessment for the use of ILE should be implemented on a case-by-case basis.
• Rhyee, S. H., Farrugia, L., Wiegand, T., Smith, E. A., Wax, P. M., Brent, J., & , T. I. (2014). The toxicology investigators consortium case registry-the 2013 experience. Journal of medical toxicology : official journal of the American College of Medical Toxicology, 10(4), 342-59.
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  The Toxicology Investigators Consortium (ToxIC) Case Registry was established in 2010 by the American College of Medical Toxicology. The Registry includes all medical toxicology consultations performed at participating sites. This report summarizes the Registry data for 2013. A query of the ToxIC Registry was carried out for the dates of January 1 through December 31, 2013. Specific data reviewed for analysis included demographics (age, gender), source of consultation, reasons for consultation, agents involved in toxicological exposures, signs, symptoms and clinical findings, and treatment. A total of 8,598 cases were entered into the Registry in 2013. Females accounted for 49.2 % of cases, males for 47.7 %, and gender was not reported in 3.1 %. The majority of patients (63.4 %) were adults between the ages of 19 and 65 years. There were 93 fatalities (1.1 %). Most referrals for medical toxicology consultation originated from the emergency department (59.7 %) or inpatient services (16.7 %). Exposures to pharmaceutical products (intentional and unintentional) made up 50.0 % of cases. Illicit drug abuse (8.0 %) and adverse drug reactions (ADRs) (4.8 %) were the next most frequent reasons for consultation. Similar to past years, nonopioid analgesics, sedative-hypnotics, and opioids were the most commonly encountered agents. Symptoms or clinical findings were documented in 71.1 % of patients. Of all cases, 54.6 % required some form of medical treatment (antidotes, antivenom, chelation, specific types of supportive care). This report serves as a comprehensive survey of medical toxicology practice within participating institutions. Prior trends continued to apply this year and indicate analgesic (opioid and nonopioid), sedative-hypnotic/muscle relaxant agents, illicit drug use, and ADRs continue to be major toxicological problems. Cases requiring medical toxicology consultation in 2013 predominantly involved pharmaceuticals and illicit drugs. Reasons for these drug exposures were diverse and included intentional overdose, unintentional exposure, withdrawal syndromes, and ADRs. Nonopioid analgesics, sedative-hypnotic agents, and opioids remained the most frequently encountered agent classes. While over half of cases required some form of medical treatment, fatalities were uncommon.
• Ruha, A., & Levine, M. (2014). Central nervous system toxicity. Emergency medicine clinics of North America, 32(1), 205-21.
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  Central nervous system toxicity caused by xenobiotic exposure is a common reason for presentation to the emergency department. Sources of exposure may be medicinal, recreational, environmental, or occupational; the means of exposure may be intentional or unintended. Toxicity may manifest as altered thought content resulting in psychosis or confusion; may affect arousal, resulting in lethargy, stupor, or coma; or may affect both elements of consciousness. Seizures may also occur.
• Ruha, A., Curry, S. C., & Levine, M. (2014). In reply. Annals of emergency medicine, 63(1), 93.
• Boyer, L., Degan, J., Ruha, A., Mallie, J., Mangin, E., & Alagón, A. (2013). Safety of intravenous equine F(ab')2: insights following clinical trials involving 1534 recipients of scorpion antivenom. Toxicon : official journal of the International Society on Toxinology, 76, 386-93.
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  The technology of antivenom production has gradually changed since the earliest production of antisera around the turn of the 20th century. Use of early antisera was associated with frequent acute adverse reactions and serum sickness. New F(ab')2 products, manufactured using pepsin degradation of immunoglobulin together with precipitation of unwanted protein and albumin serum fractions, should in concept cause fewer immune reactions in clinical use.
• Levine, M., Curry, S. C., Padilla-Jones, A., & Ruha, A. (2013). Critical care management of verapamil and diltiazem overdose with a focus on vasopressors: a 25-year experience at a single center. Annals of emergency medicine, 62(3), 252-8.
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  Verapamil or diltiazem overdose can cause severe morbidity and death, and there exist limited human data describing management and outcome of a large number of such patients. This article describes the management and outcome of patients with nondihydropyridine calcium-channel blocker overdose, with an emphasis on vasopressor dosing, at a single center.
• Levine, M., Froberg, B., Ruha, A. M., Burns-Ewald, M., Yen, M., Claudius, I. A., Arthur, A. O., Tormoehlen, L., & Thomas, S. H. (2013). Assessing the toxicity and associated costs among pediatric patients admitted with unintentional poisonings of attention-deficit/hyperactivity disorder drugs in the United States. Clinical toxicology (Philadelphia, Pa.), 51(3), 147-50.
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  Attention-deficit/hyperactivity disorder (ADHD) is widespread, with a national (United States) prevalence of nearly 10%. The 2011 changes in the diagnostic criteria will likely further increase the prevalence of this disorder. Little is known about the incidence of toxicity from unintentional poisonings of ADHD medications. This study attempted to determine the incidence of these ingestions and the corresponding financial impact in the United States.
• Ruha, A. (2013). Recommendations for provoked challenge urine testing. Journal of medical toxicology : official journal of the American College of Medical Toxicology, 9(4), 318-25.
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  "Urine mobilization test," "challenge test," and "provoked urine test" are all terms used to describe the administration of a chelating agent to a person prior to collection of their urine to test for metals. There is no standard, validated challenge test. Despite recommendations by professional and government organizations against the use of provoked urine testing, the tests are still commonly used and recommended by some practitioners. Challenge testing utilizes a variety of chelating agents, including dimercaptosuccinic acid (DMSA), dimercaptopropanesulfonate (DMPS), and ethylenediaminetetraacetic acid (EDTA). The agents are given by a variety of routes of administration, doses used are inconsistent, and urine collection procedures vary. Additional problems with challenge tests include comparison of results to inappropriate reference ranges and creatinine correction of urine obtained within hours of chelator administration. Human volunteer studies demonstrate that mercury is detected in the urine of most people even in the absence of known exposure or chelator administration, and that urinary mercury excretion rises after administration of a chelator, regardless of exposure history and in an unpredictable fashion. Studies also demonstrate that challenge testing fails to reveal a "body burden" of mercury due to remote exposure. Chelating agents have been associated with adverse reactions. Current evidence does not support the use of DMPS, DMSA, or other chelation challenge tests for the diagnosis of metal toxicity. Since there are no established reference ranges for provoked urine samples in healthy subjects, no reliable evidence to support a diagnostic value for the tests, and potential harm, these tests should not be utilized.
• Skolnik, A. B., O'Connor, A., Ruha, A., & Curry, S. (2012). Recommendations regarding management of methanol toxicity. Annals of emergency medicine, 60(6), 816-7, author reply 817.

Other Teaching Materials

• Ruha, A. (2017. How do I talk to my kids about prescription drugs and the dangers of taking opioids?. USA Today Network.