2014 ACMT Annual Scientific Meeting Research Abstracts 61-80
O'Connor AD1, Padilla-Jones A2, Ruha AM2
1Banner Good Samaritan Medical Center, Phoenix, AZ, USA; 2Center for Toxicology Pharmacology Education and Research, Banner Good Samaritan Medical Center, Phoenix, AZ, USA
Background: AAPCC data indicates there were 19,108 calls in 2011 regarding scorpion envenomation with the vast majority involving adults. The threat of scorpion envenomation to pediatric patients is well known. However, little information is available regarding adults with severe scorpion envenomation.
Research Question: Are adults with severe envenomation from Centruroides sculpturatus at risk for significant morbidity?
Methods: This is a retrospective study of adults (age > 18 years) presenting to a tertiary referral center with severe scorpion envenomation from January 1, 2007 thru March 3, 2013. Patients were identified by a search of the hospital’s electronic medical records for encounters containing ICD-9 code family “venomous animals and plants as the cause of poisoning and toxic reactions”. Patients with Grade III or IV envenomation for which medical records were available were included in the study. Descriptive statistical analysis was performed.
Results: Thirty patients met inclusion criteria, 60% were female (18/30), average age was 38.6 (20-81) years, and average time to healthcare facility was 134.3 (14-720) minutes. Signs and symptoms are summarized [Table]. Average length of stay was 27.7 (1.5-307) hours with 53% (16/30) requiring hospital admission. Two patients developed rhabdomyolysis (CK>500 IU/L). Two patients were pregnant with one requiring admission and fetal monitoring; both had good outcomes. Two patients required cardiac evaluation due to elevated troponin, chest pain, and pre-existing CAD. Two patients required intubation due to iatrogenic sedation. One had respiratory failure due to a medication error that occurred after signs of envenomation had largely resolved; this patient had evidence of aspiration on CXR. Another patient developed CNS and respiratory depression from titration of opioids and benzodiazepines necessitating two doses of naloxone and ICU transfer. The most frequently used symptom control agents were benzodiazepines 87% (26/30) and opioids 83% (25/30).
Discussion: Adults with severe scorpion envenomation often require overnight admission to control symptoms or to manage side effects of treatment. These patients may be at risk for medical errors.
Conclusion: Little information is available in the medical literature regarding adults with severe scorpion envenomation. This study suggests that this population may be at risk for significant morbidity.
Offerman SR1, Munday SW2, Wax PM3, Brent J4, Daubert GP1
1Kaiser Permanente Northern California, Sacramento, CA, USA; 2Sharp Rees-Steely Medical Group, San Diego, CA, USA; 3University of Texas Southwestern Medical Center, Dallas,TX, USA; 4Toxicology Associates, University of Colorado Health Sciences Center, Denver, CO, USA
Background: Medical Toxicology (MT) is a relatively new specialty. Little is known regarding MT practice patterns, financial compensation, or attitudes regarding compensation.
Research Question: Our aim was to survey and describe the opinions of Medical Toxicologists (MTs) regarding their practice patterns and compensation.
Methods: The ACMT practice committee conducted an anonymous, electronic survey of ACMT members regarding their practice patterns, compensation and salaries. Survey invitations were sent out by e-mail to all ACMT members in December 2012. Reminder e-mails were sent in January and February 2013. Blinded results were analyzed using simple statistics.
Results: There were 176 total respondents which represented a 49% (176/360) response rate. The most common primary specialties were Emergency Medicine (81%, 139/171), pediatrics (10%, 17/171), and internal medicine (7%, 12/171). The majority of respondents (86%, 150/175) completed a MT fellowship. Of practicing MTs, 78% identify themselves as working in academia, 64% in clinical practice, and 58% with a poison control center (PCC). The majority (59%) of MTs surveyed report spending less than half of their time on MT activities and one third (31%, 49/155) spend less than 25% of their time on MT activities. Only 16% (25/155) report practicing full-time. 7% (11/150) of surveyed Toxicologists receive full-time compensation from PCCs. 33% (49/150) provide free work to a PCCs. 46% (68/149) of MTs do not feel that they are fairly compensated for their work. 54% (85/157) would like to expand their Toxicology activities. However 87% (137/158) believe that significant barriers to expansion exist.
Discussion: Academia and PCC work are still the most common practice scenarios for MTs. Full-time MT practice is unusual. The majority of MTs spend less that half their professional time on Toxicology related activities. PCC work is common among MTs; full-time employment is unusual. Many MTs do not feel they are fairly compensated for Toxicology work. Over half would like to expand their Toxicology practice but the majority perceive significant barriers to expansion.
Conclusion: Full time practice is unusual in MT. PCC work is common, but full-time compensation is not. Many MTs do not feel that they are fairly compensated.
Onisko NS1, Wax PM2, Kleinschmidt KC2, On behalf of the ACMT Toxicology Investigators Consortium (ToxIC)
1Parkland Health and Hospital System, Dallas, TX, USA; 2University of Texas Southwestern Medical Center, Dallas, TX, USA
Background: Acetaminophen (APAP) commonly causes elevations in AST > 1000 U/L. The next most commonly implicated xenobiotics causing AST>1000 are less clear.
Research Question: What is the prevalence of non-APAP containing xenobiotics associated with AST>1000 seen by medical toxicologists?
Methods: Using the search criteria “AST>1000”, all cases entered into the Toxicology Investigators Consortium (ToxIC) database from May 1, 2012 to October 30, 2013 were reviewed. 462 cases met these criteria. 263 cases with an APAP-containing xenobiotic as primary or secondary agent of exposure were excluded. 64 cases where a xenobiotic was not specified and another 5 cases that were deemed “unlikely tox related” were also excluded. Of the remaining 130 cases, there were 95 single agent exposures and 35 multi-agent exposures. We limited our analysis to single-agent exposures for the prevalence of different xenobiotics and the clinical outcomes.
Results: Ethanol was the primary xenobiotic in 52/95 (55%) cases. Of these, 14 (27%) developed metabolic acidosis (pH < 7.2), 8 (15.3%) developed hyperreflexia, myoclonus or clonus, 5 (9.6%) developed acute kidney injury (AKI) (creatinine > 2), and 3 (5.7%) died. Opioids accounted for 9/95 (9%) cases. AKI occurred in 7 (78%) opioid cases, rhabdomyolysis (CPK > 1000) in 5 (55%) and death in 2 (22%). Methamphetamine exposures comprised 7/95 (7%) cases. Four (57%) developed AKI and 5 (71%) developed rhabdomyolysis. Mortality among this group was 14%. Overall mortality among all single-agent non-APAP cases analyzed was 9% (9). Other agents associated with death included rivaroxaban and valproic acid. Synthetic cathinones, carbamazepine, carisoprodol, acetazolamide, methimazole, risperidol and black cohash were also associated with AST > 1000.
Discussion: Ethanol was commonly associated with AST>1000 in this series although this is not typical of ethanol-induced liver injury. The high prevalence AKI in the opioid and methamphetamine patients suggested development of multisystem failure. Prospective studies on patients with AST>1000 would better characterize the mechanisms of these liver injuries.
Conclusion: Frequently abused xenobiotics including ethanol, opioids and methamphetamine accounted for the most non-APAP associated AST>1000 cases seen by medical toxicologists.
Onisko NS1, Kleinschmidt KC2, Forrester MB3
1Parkland Health and Hospital System, Dallas, TX USA; 2University of Texas Southwestern Medical Center, Dallas, TX, USA; 3Texas Department of State Health Services, Austin, TX, USA
Introduction: In July 2013, the FDA issued a black box warning for mefloquine relating to acute neuropsychiatric events (NSEs). Numerous case reports exist pertaining to neuropsychiatric events in the literature, however, our literature review did not find any larger case series.
Hypothesis: The prevalence of NSEs among patients reporting adverse events (AEs) related to mefloquine is low and that the most common AE would be the very non-specific “headache.”
Methods: Using the search term “mefloquine”, all cases entered into the Texas Poison Center Network (TPCN) database from January 1, 2000 to June 1, 2013 were reviewed. The codes for all AEs were assessed. The individual charts for all cases that included a code for NSEs were reviewed in detail. Patients with coingestions were included.
Results: Fifty-six mefloquine cases were identified. Fifty-two percent were male. The ages: 55% were ≥ 20, 12.5% were 6-9 and 30.4% were 0-5. The most common symptoms were all gastrointestinal, nausea (10.7%), diarrhea (8.9%) and abdominal pain (7.1%). Neuropsychiatric symptoms were identified in 9 (16%) cases, all were single agent exposures. Among the 9 cases, dizziness occurred in 5, confusion in 3, headache in 2, agitation in 2 and visual hallucinations in 1. The number of tablets ingested ranged from 1-7. The duration of exposures ranged from a single one to the pills taken over one week. Medication dosing errors occurred in 4 of these 9 cases because the patients took the medication daily instead of weekly.
Discussion: While the most common AEs associated with mefloquine were gastrointestinal, the neuropsychiatric symptoms were more commonly reported than what we expected. Also, the symptoms included confusion and hallucinations. Headache, while present, was not very common. Interestingly, 4/9 patients with NSEs had mistakenly taken the medicine daily vs. the prescribed weekly regimen, reflecting the ease in which this medicine can be taken inappropriately.
Conclusion: Mefloquine related neuropsychiatric symptoms occurred in 16% of the reported cases and the most common NSE was dizziness.
Ordonez J1, Forrester MB2, Wax PM3, Kleinschmidt KC3, On behalf of the ACMT Toxicology Investigators Consortium (ToxIC)
1Parkland Health and Hospital System, Dallas, TX , USA; 2Texas Department of State Health Services, Austin, TX, USA; 3University of Texas Southwestern Medical Center, Dallas, TX, USA
Background: Acetaminophen (APAP) exposures are common in toxicology. The data from these exposures have been traditionally registered in the National Poison Data System (NPDS). This database has been the main source of epidemiological information about toxicological problems. However, in 2010, the American College of Medical Toxicology (ACMT) created the Toxicologic Investigators Consortium (ToxIC) in order to register cases seen by Medical Toxicologists (MT) at the bedside.
Study question: Do APAP cases reported in the ToxIC registry have more serious clinical presentations than those in the NPDS?
Methods: This is a comparative study of demographic and clinical data of acetaminophen exposures in the ToxIC registry with the Texas Poison Center Network (TPCN) database from January 1, 2010 to October 30, 2013. While not all of the data from the TPCN database are downloaded into NPDS, much is, and it thus reflects the total NPDS to a reasonable degree. The clinical information analyzed included all cases with hepatotoxicity, coagulopathy, acute kidney injury, liver function test abnormalities, hepatic necrosis and hepatitis.
Results: In the ToxIC registry, we identified 2787 (11%) acetaminophen cases from 24,609 total exposures vs 44,241 acetaminophen cases (7%) from 640,946 total exposures in TPCN database. 22% of the acetaminophen cases in the ToxIC registry had hepatotoxicity vs 2% in the TPCN database. NAC was administered in 69% of ToxIC patients vs 17% in TPCN. The table has other comparisons.
Discussion: Hepatotoxicity, coagulopathy and acute renal injury were more commonly seen in ToxIC registry than TPCN cases and NAC was more frequently given in the ToxIC registry than TPCN database. A limitation is differences in coding between these two databases.
Conclusion: APAP exposed patients in the ToxIC registry are more severely poisoned than those in the TPCN database.
East Carolina University, Greenville, NC, USA
Background: Carbon dioxide is a colorless, odorless gas with poor warning properties. Deaths from exposure are probably uncommon, but there are numerous reports in the literature and media. There has been no attempt to identify these cases systematically to assess the burden of mortality from carbon dioxide poisoning in the US. This is likely difficult to do because of diverse reporting mechanisms.
Research Question: What is the incidence of carbon dioxide associated fatalities in the US between 1/1/2000 and 12/31/2011?
Methods: This is a retrospective review of multiple databases to identify fatalities associated with carbon dioxide from 2000-2011. We will manually review the annual reports from the National Poison Data System (NPDS), using defined search criteria. We will search PubMed and Web of Science for cases published in the literature, search the LexisNexis database for print news articles, and search the National Electronic Injury Surveillance System (NEISS). All results will be reviewed by a medical toxicologist for duplicate or improperly classified cases.
Results: We identified 5 deaths in NPDS, 6 deaths in the literature, 124 news articles, and 0 deaths in NEISS. Three deaths from the literature search were excluded because of improper classification. There were 124 news articles, however many described the same case or actually referred to carbon monoxide instead; excluding these left 16 fatalities. Of these 16, 2 described cases reported in NPDS and 1 was from the literature search. Reported ages of the 21 total unique cases ranged from 19 to 80 years, and included an extremely wide range of circumstances ranging from a fast food restaurant bathroom carbon dioxide leak to being locked in a room when the carbon dioxide based fire suppression system was triggered. 16 deaths (69.5%) were unintentional and 12 (52%) were occupational. 5 incidents involved multiple deaths.
Discussion: The news media database yielded the most cases, many of which were not reported in other databases. Many deaths were unintentional and occurred at work.
Conclusion: We identified 21 unique cases of carbon dioxide associated fatalities in the United States in an eleven year time period with a very diverse situation for nearly every fatality.
Radke JB1,2, Chenoweth JA1,2, Ford JB1, Sutter ME1
1University of California, Davis, Sacramento, CA, USA; 2Veterans Administration Northern California Health Care System, Mather, CA, USA
Background: Tricyclic antidepressants cause predominantly cardiovascular and neurologic toxicity. Onset of symptoms is rapid in overdose,and is often seen within the first 1-2 hours.
Hypothesis: Pill bezoars can significantly alter onset and peak symptoms in overdose.
Methods: A 53 year old male with a history of hypertension and diabetes presented to the emergency department (ED) with altered mental status. The patient’s sister at bedside said that his regular medications included metformin, glyburide, aspirin, prasurgrel, and metoprolol. The patient had several episodes of emesis the night prior, but was otherwise normal. His wife tried to wake him in the morning and noted that he was confused, with slurred speech, so she called emergency medical services and he was brought to the ED around 1000 hr. The initial electrocardiogram (ECG) showed sinus tachycardia with a rate of 118 bpm, QRS of 116 ms with no tall R wave in aVr. There were no prior ECG’s for comparison. A sodium bicarbonate bolus was given without change in the QRS duration. The patient became more obtunded and was intubated at 1600 hr. He had a generalized tonic-clonic seizure at 1630 despite optimal ventilation. The patient received a CT scan of his abdomen which revealed a large amount of hyperdense material resembling pills in his stomach. The patient continued to have a prolonged QRS (peak of 138 ms) and was therefore started on sodium bicarbonate therapy. Gastroenterology was consulted for an EGD to extract the pills. He was treated with activated charcoal and whole bowel irrigation after the EGD to limit toxicity of the remaining pills.
Results: Urine GC/MS and whole pill identification was positive for clomipramine. His tachycardia gradually improved, as did his QRS, which was
Discussion: Tricyclic antidepressants are one of the few drugs where we have both pharmacokinetic and toxicokinetic data. However, this case illustrates a clinical scenario where toxicokinetic data did not predict the clinical course.
Conclusion: Pill bezoars can cause a delay in onset of significant toxicity after tricyclic antidepressant overdose, as well as prolonged toxicity.
Reid NE1, Mazer-Amirshahi M2,3, Litovitz TL1,4
1National Capital Poison Center, The George Washington University, Washington, DC, USA; 2The George Washington University, Washington, DC, USA; 3Children's National Medical Center, Washington, DC, USA; 4Georgetown University, Washington, DC, USA
Background: Certain metal-on-metal (MoM) hip prostheses have been associated with increased wear and deterioration resulting in chronic cobalt exposure. There have been reports of elevated cobalt concentrations and early prosthesis failure in patients with MoM implants, however, systemic cobalt toxicity is rare in this setting.
Hypothesis: Chronic cobalt exposure from MoM prostheses can result in non-ischemic cardiomyopathy.
Methods: This is a single patient chart review. A 63-year-old man with a prior history of deep vein thrombosis, peptic ulcer disease, hypertension and dyslipidemia underwent a total hip athroplasty, receiving a MoM prosthesis. Three years later, he was admitted to the hospital with decompensated heart failure with an ejection fraction of 10-15%. During the previous year, the patient had progressive shortness of breath and exercise intolerance and was diagnosed with non-ischemic cardiomyopathy after an extensive work-up, including cardiac catheterization and biopsy. Cobalt concentrations were obtained given the history of MoM prosthesis.
Results: The peak measured urine cobalt concentration was 202 mcg/L (reference range 0.1-2 mcg/L) and was felt to be contributory to the development of the patient’s cardiomyopathy. The patient also had a urine chromium concentration of 57.6 mcg/L (reference range 0-10 mcg/L). Orthopedics was consulted for potential removal of the prosthesis, but the patient had developed renal failure and S. aureus sepsis and was not stable for surgery. The patient underwent chelation therapy with succimer, which decreased his measured urine cobalt concentration to 11 mcg/L. Subsequently he developed an arterial thrombus in the lower extremity, which required operative removal and fasciotomy. He was placed on extracorporeal membrane oxygenation (ECMO) due to hemodynamic instability. The patient had a biventricular assist device placed, but ultimately expired.
Discussion: Although this patient was treated with succimer and urine cobalt concentrations were successfully reduced, there was no improvement in the patient’s clinical condition. Clinical recovery may not have been possible, as many of the pathophysiologic manifestation of cobaltism are often irreversible.
Conclusion: Systemic toxicity, including cardiomyopathy may occur pursuant to chronic cobalt exposure from MoM prosthesis.
Ruha AM1, Levitan R1, Kleinschmidt KC2, Vohra R3, Smith E2, Brent J4, Wax PM2, On behalf of the ToxIC Snakebite Study (TICSS) group
1Center for Toxicology and Pharmacology Education and Research, Phoenix, AZ, USA; 2University of Texas Southwestern Medical Center, Dallas, TX, USA; 3UCSF Fresno Medical Center, Fresno, CA, USA; 4Toxicology Associates, University of Colorado Health Sciences Center, Denver, CO, USA
Background: Snakebite affects thousands of people in the US annually, and can cause significant morbidity and mortality. Despite the large impact on victims, current understanding of venom pathophysiology, predictors of severity, treatment strategies, and long-term outcome is limited. The Toxicology Investigators Consortium (ToxIC) North American Snakebite Registry (NASBR) was established to collect de-identified data regarding all aspects of snake envenomation.
Research Question: Can the NASBR serve as a research tool to collect a large amount of data from multiple toxicology centers across the US?
Methods: Data reported to the NASBR between March 1 and October 24, 2013 were reviewed. Results are reported using descriptive statistics.
Results: 8 sites representing 7 states across the US contributed 96 cases. One non-native bite was excluded. Of 95 subjects, 72% were men. 69% were age 13 - 65 years, 9% 65 years. 40% had co-morbidities. 6% had acute ethanol exposure. Bites were from 61 rattlesnakes, 22 copperheads, 2 cottonmouths, and 10 unknown crotalids. 45% were upper extremity and 55% lower extremity bites. 93% demonstrated swelling and 35% erythema, 9% received prophylactic or empiric antibiotics. 39% had hemotoxicity, 4 had minor early bleeding. 15% had bullae or necrosis. 5% had neurotoxicity. 6 patients had a tourniquet placed. 84% received antivenom. 6 patients received prophylaxis against antivenom reaction. 7 (9%) adverse reactions to antivenom were reported. 6 procedures were performed, including 4 wound debridements and 2 fasciotomies. 39% of patients had at least one set of follow-up labs. One patient was readmitted 2 days post-bite for worsening thrombocytopenia and bleeding. Three additional patients were admitted 4-7 days post-bite, all with late thrombocytopenia and two with complete defibrination. One was admitted a third time 15 days post-bite for a second thrombocytopenia recurrence.
Discussion: These data provide a nationally representative sample of snakebite victims seen at the bedside by medical toxicologists. The registry provides a unique opportunity to study numerous aspects of snake envenomation, including at-risk populations, rare effects, unusual treatments, and relationship between patient factors, severity and outcomes.
Conclusion: The NASBR is a powerful tool for gathering and studying a vast amount of information related to snakebite.
*On behalf the ToxIC Snakebite Study (TICSS) group: Anna Arroyo-Plascencia, Vikhyat S. Bebarta, Michael Beuhler, Adam Bosak, Jeffrey Brent, Daniel Brooks, E. Martin Caravati, Steven Curry, William Dribben, Kimberlie Graeme, S. Eliza Halcomb, C. William Heise, Janetta Iwanicki, William Kerns, Thomas Kibby, Kurt Kleinschmidt, Michael Levine, Rachel Levitan, Frank LoVecchio, Michael E. Mullins, Ayrn O’Connor, Angie Padilla-Jones, Anne-Michelle Ruha, Evan S. Schwarz, Aaron Skolnik, Eric Smith, An Tran, Shawn M. Varney, Rais Vohra, Paul Wax
Rushton WF, Dabrowski KH, Vakkalanka JP, King JD, Charlton NP
University of Virginia, Charlottesville, VA, USA
Introduction: Snakebites are a common complaint of emergency department visitors. From 2008 to 2010, there were 19,746 human exposures to venomous snakes in the United States (U.S.) and in 2011 alone, there were 6,630 snakebite cases reported to the American Association of Poison Control Centers. Review of the literature demonstrates only a few cases of an embedded snake foreign body (FB). However, in addition to standard treatment, numerous reputable sources for health care providers advocate for routine imaging to rule out a snake foreign body.
Methodology: A Toxicall database at a regional poison center serving a population of 2.8 million people was queried for all records indicating a snakebite from January 2003 through June 2013. Results were then searched using the free text section in the notes field for the following terms: ‘fang’, ‘tooth’, ‘teeth’, ‘x-ray’, ‘xray’, and ‘x ray’. As a snake tooth or fang were anticipated to be the key foreign bodies identified on x-ray imaging, variations of these terms were used in the search criteria. Each chart that had at least one of these terms was independently reviewed for the presence or absence of a foreign body.
Results: The query returned 1,679 charts indicating a snakebite, of which 11% (n=183) contained one of the aforementioned search terms. Review of these charts did not result in any cases with a retained foreign body.
Conclusion: Snakebites are a common presenting problem in U.S. emergency departments. Our review found no instances of retained foreign body in snakebites occurring between 2003 and June 2013. Based on the data from this poison center, we propose that snakebites do not require routine imaging to evaluate for retained foreign bodies as this is an exceedingly rare occurrence.
Simmons JC, Rushton WF, King JD, Charlton NP
University of Virginia, Charlottesville, VA, USA
Background: Serotonergic agents have become ubiquitous throughout medical care and include drugs such as selective serotonin reuptake inhibitors (SSRI), monoamine oxidase inhibitors, select opioids (tramadol, fentanyl, and meperidine), antimicrobials (linezolid), over-the-counter preparations (dextromethorphan), lithium, and drugs of abuse (MDMA, LSD, cocaine, mushrooms). Despite the frequent prescribing pattern of serotonergic medications, medical students have often been unable to identify serotonergic medications during their Medical Toxicology rotation. The object of this study is to determine if senior medical students are cognizant of drugs that have high serotonergic activity and could potentiate serotonin syndrome.
Methods: A clinical vignette regarding an adolescent male who daily takes an SSRI and who presented with fulminant serotonin syndrome after abusing dextromethorphan was distributed to a fourth year medical school class at one institution. Students were given a list of drugs commonly used in the ICU setting and asked to identify which were known to increase serotonergic activity and thus be avoided in the management of this patient. Response to the survey was entirely voluntary and two reminder emails were sent to increase responses.
Results: 120 participants replied out of a class of 155 for a 77.4% response rate. The following agents were correctly identified for their potential to increase serotonergic activity: sertraline, 87.5%, meperidine, 50.8%, linezolid, 35.8 %, fentanyl, 18.3%, and lithium, 16.7%. The following agents were incorrectly identified as worsening serotonin syndrome: quetiapine, 45%, dexmedetomidine, 12.5%, propofol, 5%, midazolam, 3.3%, and cefepime, 0%.
Discussion: Our results demonstrate significant gaps in understanding of serotonergic agents among fourth year medical students. While 87.5% were able to identify that sertraline would worsen the syndrome, only 50% identified meperidine as serotonergic despite the historical implications of this interaction. Also concerning was the belief that quetiapine had serotonin agonist activity, reflecting failure to understand the mechanism of this commonly prescribed xenobiotic.
Conclusion: Senior medical students require increased education on the pharmacology of commonly used serotonergic drugs in the ICU setting to avoid worsening serotonin syndrome or causing an iatrogenic adverse drug reaction.
Sinha M, Quan D, McDonald FM, Valdez A
Arizona Children's Center, Maricopa Integrated Health System, Phoenix, AZ, USA
Objective: Recently, an effective antivenom for clinically significant scorpion envenomation has been approved by FDA and is being increasingly used in emergency departments across the country, but no formal economic analysis on its impact on cost of management of these patients has been performed.
Methods: Three different strategies of clinical management of scorpion envenomation with systemic neurotoxic symptoms in pediatric patients were compared for cost-minimization from a third-party-payer perspective. In strategy I, patients with clinically significant scorpion envenomation with cranial nerve dysfunction and/or somatic skeletal neuromuscular dysfunction were managed with supportive care only and without use of scorpion antivenom. In strategy II, an aggressive strategy of full-dose Anascorp® antivenom (initial dose of three vials with the use of additional vials administered one vial at a time) was considered. In strategy III, a single-vial serial dosing strategy of Anascorp® titrated to clinical response was considered. Clinical probabilities for the different strategies were obtained from retrospective review of medical records of patients with scorpion envenomation over a 10-year period at our institution, and from published information. Baselines cost values were obtained from patient reimbursement data from our institution. Indirect costs were not considered in this analysis.
Results: In the baseline analysis, strategy I of supportive care only with no antivenom was the least costly at $3,466.50 per patient. Strategy III of single-vial serial dosing was intermediate but less expensive than strategy II of full-dose antivenom, with an incremental cost of $3,171.08 per patient. In a one-way sensitivity analysis, at a threshold antivenom cost of $1,577.87, strategy III of single-vial serial dosing became the least costly strategy.
Conclusion: For children with scorpion envenomation with neurotoxic symptoms, use of a management strategy based on serial dosing of Anascorp® titrated to clinical response is less costly than a strategy of initial use of full dose antivenom. Also, lowering the cost of antivenom would make use of titrated antivenom dosing in all children with significant neurotoxic symptoms the most favored strategy even compared to the strategy of conservative management without use of antivenom.
Smith RB1, Swartzentruber GS2, Richardson WH1,3
1Palmetto Health Richland, Columbia, SC, USA; 2University of Pittsburgh Medical Center, Pittsburgh, PA, USA; 3Palmetto Poison Center, Columbia, SC, USA
Background: Intravenous injection of reformulated Opana ER® has recently been described to cause hemolytic anemia and thrombotic thrombocytopenic purpura (TTP) in a 2012 report by the Tennessee Department of Health. TTP is a relatively rare hematologic condition characterized by microangiopathic hemolytic anemia and widespread activation of the coagulation cascade, leading to coagulopathy, consumption of platelets and resulting in end-organ damage.
Hypothesis: Intravenous administration of the newest reformulation of Opana ER® (Endo Pharmaceuticals Inc.) has potential to cause hemolytic anemia and TTP.
Methods: This is a chart review of two patients. A 40 year-old female presented to the emergency department with one month of progressive, generalized weakness, dyspnea, and jaundice. She admitted to crushing and intravenously injecting Opana ER®. Laboratory studies revealed anemia, thrombocytopenia, acute renal failure and coagulopathy. Hemolysis was signified by markedly elevated LDH and schistocytes on blood smear. She required sixteen sessions of plasmapheresis, high-dose methylprednisolone, and blood transfusions. One month prior, her 46 year-old husband was admitted with two weeks of generalized fatigue, nosebleeds, confusion, blurry vision, and dyspnea on exertion. Laboratory studies revealed anemia, thrombocytopenia, elevated troponin and markedly elevated LDH. Peripheral smear demonstrated helmet cells and schistocytes. He responded to plasmapheresis and was discharged only to be readmitted three days prior to his wife for an early relapse of TTP. In total he required 18 plasma exchanges.
Results: Review of two patient charts reveals diagnoses consistent with hemolytic anemia and TTP. Standard therapy for TTP resulted in eventual normalization of hematologic parameters.
Discussion: Two cases of TTP are described in individuals who admitted to crushing and injecting reformulated Opana ER®. Review of records and history is negative for other known causes of TTP. The mechanism by which this occurred is unknown. Proposed mechanisms include the effects of abuse-preventing inactive ingredients which are found in the newest reformulation. A comparison of inactive ingredients is made (Table). Cases of TTP have not been linked to older formulations of Opana ER® suggesting a mechanism unique to the newest formulation.
Conclusion: Hemolytic anemia and thrombotic thrombocytopenic purpura may occur following the intravenous injection of reformulated Opana ER®.
Srisuma S1,2, Lavonas EJ1, Wananukul W2
1Rocky Mountain Poison and Drug Center, Denver, CO, USA; 2Ramathibodi Poison Center, Mahidol University, Bangkok, Thailand
Background: Although uncommon, severe ergotism continues to occur in Thailand. We sought to determine the precipitating factors and clinical manifestations of these cases.
Method: This is a retrospective cohort study of all patients with ergotism consulted to Ramathibodi Poison Center Bangkok Thailand from January 2006 to August 2013. Cases were identified by substance codes and data were abstracted by poison center senior scientist.
Result: Twelve cases of ergotism were identified. Patient ages ranged from 15 months to 50 years. Nine patients were female. All cases were associated with ergotamine 1 mg / caffeine 100 mg combination tablets. Nine cases (75%) were precipitated by drug-drug interactions with CYP 3A4 inhibitors: lopinavir/ritonavir (8 cases) and erythromycin (1 case). In none of these cases was overdose suspected. The other cases involved suicidal intent (2 cases) and accidental ingestion (1 case).Ten patients had vascular insufficiency symptoms including cooling, numbness, pain, and pulse deficit in distal limbs, treated with vasodilators and anticoagulants. Five of these patients initially had low or unmeasurable blood pressure by non-invasive technique which resolved after intravenous vasodilator administration. One patient died from rhabdomyolysis and acute renal failure, two underwent partial foot amputations due to lower extremity gangrene, and seven patients recovered fully. Two patients did not develop vascular insufficiency symptoms. One was a 15 month old boy with unsupervised ingestion of an unknown dose presented with alteration of consciousness and seizure. He was intubated, treated with diazepam and phenobarbital. He died on the next day. Another case was 14 year old female who ingested 100 tablets with suicidal intent. She presented with vomiting and recovered with supportive care.
Discussion: Severe ergotism cases continue to occur in Thailand. Most cases are caused by interaction with CYP3A4 inhibitors, which increase ergotamine bioavailability at least 4 fold. Factitious low blood pressure in these cases was caused by severe vasospasm. The severe symptom in 15 month old case may be from poor metabolism of ergotamine and caffeine due to immature of CYP3A4 and 1A2 respectively.
Conclusion: Severe ergotism can be precipitated by drug interaction and present with factitious hypotension caused by profound vasospasm.
Steck AR, Al-Mulhim K, Geller RJ, Hon S, Kazzi ZN
Georgia Poison Center, Emory University, Atlanta, GA, USA
Background: Intravenous (IV) vancomycin is an antibiotic with a narrow therapeutic index and the potential for nephrotoxicity and ototoxicity. Risk factors for toxicity include a prolonged course of treatment (>7 days), elevated trough level (>20 mg/L), and pre-existing renal disease. Vancomycin has a molecular weight of 1485 Daltons, a volume of distribution of 0.39 L/kg, is 30% protein-bound, and is cleared primarily via glomerular filtration.
Case Report: A 10-year-old, 46 kg male with severe eczema was admitted for treatment of cellulitis caused by multi-drug-resistant Staphylococcus aureus. His initial renal function was normal (BUN/Cr = 4 mg/dL/0.6 mg/dL), and he was started on vancomycin 1 gram IV every 8 hours. The first vancomycin serum trough level was 14 mg/L (therapeutic range: 10 – 20 mg/L) on hospital day 2. No further monitoring was performed until hospital day 6, when the patient developed vomiting and oliguria. He was found to have acute renal failure with a BUN/Cr 21 mg/dL/3.4 mg/dL and a random serum vancomycin level of 160 mg/L. No other etiology of his renal injury was identified, although he had received a single dose of ibuprofen on the preceding day. Per the recommendations of the poison center, the patient was transferred to a pediatric tertiary care hospital, where continuous venovenous hemofiltration (CVVH) was performed with an HF 1200 filter (Medivators, Inc.) at a flow rate of 100 mL/min for 16.5 hours. During CVVH, the renal function improved and the vancomycin level declined to 38.9 mg/L. Using a first-order elimination model, the vancomycin half-lives were estimated to be 53 hours before CVVH and 9 hours during CVVH. After hemofiltration, the patient’s renal function continued to improve, and he was discharged with outpatient nephrology follow-up.
Conclusion: Supratherapeutic vancomycin levels can lead to acute renal toxicity or can be exacerbated by primary renal injury. The primary mechanism underlying this patient’s toxicity is not known. CVVH performed with a large-pore membrane appears to enhance the clearance of vancomycin and decrease its serum elimination half-life.
Stephani JA, Hendrickson RG
Oregon Health & Science University, Portland, OR, USA
Background: National and statewide laws to control methamphetamine precursors including pseudoephedrine have been enacted to decrease clandestine lab manufacture and subsequent availability/use of methamphetamine. In 2006, Oregon enacted a law requiring a prescription to obtain pseudoephedrine. No such law exists in Washington, which is thought to share similar sources of methamphetamine. The short and long-term effect of Oregon’s statewide pseudoephedrine law on methamphetamine-related deaths is unknown.
Hypothesis: The 2006 Oregon law requiring a prescription for pseudoephedrine was associated with short and long-term decreases in methamphetamine-related deaths.
Methods: Data on drug-related deaths from 2003-2012 was obtained from the Medical Examiner Offices of Multnomah County, Oregon including Portland, and from King County, Washington including Seattle. Methamphetamine-related deaths from the 3-year period immediately before the enactment of the law (2003-2005) were compared to deaths in the short term (2007-2009) and longer term (2010-2012). The rates of change in deaths were then compared between the two similar metropolitan areas.
Results: When comparing years immediately preceding (2003-2005) and immediately following (2007-2009) the law, there was a nonsignificant decrease in methamphetamine-related deaths in both Multnomah County [-4 (-14%), 95%CI-21,29, p=0.591] and King County [-4 (-17%), 95%CI-19,26, p=0.552]. When comparing 2003-2005 to later years (2010-2012), there was a nonsignficant increase in methamphetamine-related deaths in both Multnomah County [5 (19.5%), 95%CI-14,24, p=0.383] and King County [5 (22.7%), 95%CI-9,19, p=0.260)]. There was no significant difference between deaths in Multnomah and King counties in the short term [RR 0.98 (95%CI-0.79,1.23), p=0.910] or long term [RR 1.05 (95%CI-0.79,1.29), p=0.905]
Discussion: A 2006 Oregon law that required a prescription for pseudoephedrine was associated with no change in short or long-term methamphetamine-related deaths compared to a similar county in a neighboring state that did not enact a law. The years immediately following the law were associated with a short-term decrease in methamphetamine-related deaths, but a similar trend was also seen in King County, Washington, suggesting alternative variables may have been contributing, including national legislation or changes in the methamphetamine source, purity and price secondary to the decrease in methamphetamine labs.
Conclusion: The Oregon law restricting pseudoephedrine as prescription-only was not associated with a decrease in methamphetamine-related deaths.
Stephani JA, Hendrickson RG
Oregon Health & Science University, Portland, OR, USA
Background: Multiple national and statewide laws to control methamphetamine precursors including pseudoephedrine have been enacted to decrease clandestine lab manufacture and subsequent availability/use of methamphetamine. In 2006, Oregon enacted a law requiring a prescription to obtain pseudoephedrine. No such law exists in Washington, which is thought to share similar sources of methamphetamine.
Hypothesis: That the 2006 Oregon legislation restricting pseudoephedrine decreased poison center calls in Oregon, but not Washington.
Methods: Methamphetamine-related calls involving human exposures from OPC and WPC were evaluated from 2003-2012 and adjusted for population. Methamphetamine-related calls from 2003-2005 were used for comparison as pre-law call volume. The number of pre-law calls was compared to calls in the short term (2007-2009) and longer term (2010-2012).
Results: Both the OPC and WPC had a statistically significant decrease in methamphetamine-related calls in the immediate post-law period [OPC -89 calls (-62%), 95%CI -56,-121 calls, p=0.007], [WPC -74calls (-55%), (95%CI, -36,-112), p=0.014)]. However, by the later period (2010-2012), call volumes returned to their pre-law volumes [OPC, -14 (-10%), (95%CI -24,53), p=0.260, WPC, +13 (+10%), (95%CI, -60,30), p=0.349). There was no difference between the change in volume in OR and WA in the short term (RR 1.05, (95%CI, 0.978, 1.13), p=.166), whereas in the long term OPC’s call volume decreased 10% and WPC’s call volume increased 10%, a difference that was statistically significant (RR 1.10, (95%CI, 1.002, 1.21), p=0.044).
Discussion: The initial decrease in methamphetamine-related poison center calls was seen in both Oregon and Washington, indicating that a possible confounding variable may have contributed to decreased methamphetamine-related calls. The initial decrease may represent a decline in methamphetamine use in the community or a change in potency/price resulting in decreased hospital admissions or emergency department visits. However, over a longer period, the call volume of both centers increased to levels similar to those in the pre-law periods, though Oregon call volumes remained decreased in the long term compared to Washington calls.
Conclusion: A law restricting pseudoephedrine in Oregon was associated with a small long-term decrease in methamphetamine-related poison center call volume in Oregon compared to Washington. In the short term, the law was associated with a decrease in methamphetamine-related calls in both states.
Stephani JA, Hendrickson RG
Oregon Health and Sciences University, Portland, OR, USA
Background: The western states of Washington, Oregon, and California have seen a decrease in the number of clandestine labs after implementation of national and statewide regulations to control methamphetamine precursors, including pseudoephedrine. In September 2006, an even more restrictive law was enacted in Oregon requiring a prescription to obtain pseudoephedrine, which is not a part of Washington or California law. The effect of this law on methamphetamine use and subsequent admissions to rehabilitation treatment centers for methamphetamine abuse is unknown.
Hypothesis: The 2006 Oregon law requiring a prescription to obtain pseudoephedrine was associated with a change in treatment admissions for methamphetamine abuse as compared to neighboring states without similar laws.
Methods: The Treatment Episode Data Set (TEDS) from the Substance Abuse and Mental Health Services Administration (SAMHSA) was evaluated for Oregon, Washington, and California from 2003-2009. The number of admissions to rehabilitation centers for methamphetamine abuse from 2003-2005 was compared to post-legislation admissions from 2007-2009 in Oregon, Washington and California.
Results: In Oregon, there were 683 admissions/100,000 population to methamphetamine treatment centers from 2003-2005 and 592 admissions from 2007-2009, representing a decrease in admissions by 13% after enactment of the legislation. In the same time period, the rate of admissions to rehabilitation centers for methamphetamine abuse in California decreased by 6% and in Washington increased by 1% (CA and WA=3.9%). There was no statistically significant difference when the rate of change of Oregon admissions was compared to Washington and California [RR=1.051 (95%CI 0.978,1.129)].
Discussion: The 2006 law in the state of Oregon restricting pseudoephedrine to prescription-only had no significant effect on treatment admissions for methamphetamine. Future research may be directed at determining which other factors, such as drug purity or price or the source of methamphetamine(e.g. local production versus Mexico) may have on treatment admissions.
Conclusion: Restricting pseudoephedrine to prescription-only in the state of Oregon had no effect on methamphetamine treatment admissions.
Stephani JA, Hendrickson RG
Oregon Health and Sciences University, Portland, OR, USA
Background: Multiple national and statewide laws have been enacted to control the precursors for clandestine manufacture of methamphetamine. Currently, Oregon and Mississippi are the only states to require a prescription to obtain pseudoephedrine. A decrease in clandestine methamphetamine lab incidents has been demonstrated after enactment of these laws in these states, but it is unclear if other comparable states were seeing a similar decrease, suggesting possible national or regional confounding variables.
Hypothesis: There was a more significant decrease in methamphetamine lab incidents in Oregon and Mississippi as compared to surrounding states without a law requiring a prescription for pseudoephedrine.
Methods: DEA data on number of clandestine laboratory incidents by state was evaluated from 2004-2012. The Oregon law was enacted in 2006, and the number of labs in Oregon was evaluated for the period before the law (2004-2005) and compared to lab incidents in the short-term (2007-2008) and long-term (2011-2012). The rates of change in number of lab incidents were compared to neighboring states Washington and California. Mississippi lab incidents were evaluated from 2008-2009 before the law was enacted in 2010, and compared to post-implementation period(2011-2012). The number of labs in Mississippi was compared to neighboring states Louisiana, Alabama, Arkansas, Missouri and Tennessee.
Results: Total methamphetamine lab incidents in Oregon decreased significantly more than Washington and California (90% vs. 64%) in the two years after the legislation [RR=1.24 (95%CI 1.210,1.275)]. Over the longer-term, methamphetamine lab incidents in Oregon decreased significantly more than Washington and California (98% vs. 95%) over the nine year period from 2004-2012 [RR=1.024 (95%CI 1.011,1.037)]. Mississippi methamphetamine lab incidents decreased significantly more than the surrounding states (76% vs. 38%) of Tennessee, Arkansas, Alabama, Louisiana, and Missouri [RR=1.310 (95%CI 1.278,1.344)]
Discussion: Pseudoephedrine legislation was associated with a significant reduction of methamphetamine lab incidents in both states when compared to neighboring states. There was significant heterogeneity between states in the incidence of methamphetamine labs over the nine-year study period.
Conclusion: Legislation in both Oregon and Mississippi that restricted pseudoephedrine to prescription-only decreased methamphetamine laboratory incidents when compared to surrounding states without such legislation.
Stevenson JW1, Minns AB2, Smollin C2, Albertson TA2, Cantrell FL2, Clark RF1, 2
1UCSD School of Medicine, San Diego, CA, USA; 2California Poison Control System, San Diego, CA, USA
Background: Dabigatran and rivaroxaban are newer anticoagulants being used more commonly in clinical practice. Cases of bleeding have been reported with use of these agents since approval. We performed an observational case series to characterize the presentation and outcome of exposures to these medications.
Methods: Combined retrospective and prospective case series of exposures to dabigatran and rivaroxaban reported to our poison control system. Retrospective cases were identified between 1/11 to 5/12. Prospectively collected cases were collected from 5/12 to 7/13. Miscoded cases and those with possible warfarin coingestion were excluded. Other cases of co-ingestion were included. Main data variables collected included demographics, outcome, disposition, nature of exposure, treatments received, and laboratory parameters.
Results: 57 total cases were identified, with 7 excluded, leaving 37 dabigatran and 12 rivaroxaban cases for analysis. Children age 12 or less accounted for 5 dabigatran and 2 rivaroxaban cases. Bleeding was reported in 15 dabigatran cases. There were 4 cases of acute self-harm overdose with dabigatran ranging from 1800-3900 mg. Mild bleeding was reported in only one of these overdose cases and there were no deaths in this group. There were 2 fatal hemorrhages in dabigatran cases, both in patients chronically on this medication. Coagulation parameters were abnormal in many cases and did not correlate well with bleeding or outcome. Bleeding was reported in 5 rivaroxaban cases, all in patients with chronic exposure to the drug without known overdose. No cases of intentional self-harm overdose of rivaroxaban were reported, and there were no deaths. None of the pediatric cases from either group had adverse outcomes or bleeding.
Discussion: Adverse bleeding will continue to rise with exposures to the newer oral anticoagulants. Our data demonstrated that chronic dosing of these agents resulted in more episodes of bleeding than intentional overdose or excess dosing. Accidental pediatric exposures also resulted in few effects and no episodes of bleeding.
Conclusion: This case series of dabigatran and rivaroxaban exposures demonstrated the greatest degree of risk of adverse events in patients chronically taking these medications irrespective of excess dosing. Acute self-harm ingestions and accidental pediatric ingestions in our series had few adverse effects.