Faculty Bibliography

Objective: This study was designed to determine the fatality rate of suspected cyclopeptide-containing mushroom ingestions reported to the National Poison Data System (NPDS).Background: Although silibinin reportedly improves survival in suspected cyclopeptide-containing mushroom ingestions, the greater than 20% untreated fatality rate that is often cited is based on decades-old data. An ongoing open-label silibinin trial will likely use historical cases as comparators. A recent single poison control center (PCC) study showed a fatality rate of 8.3%. This study was designed to validate those findings in the NPDS.Methods: This study was an 11-year (1/1/2008-12/31/2018) retrospective review of suspected cyclopeptide-containing mushroom ingestions reported to NPDS. Inclusion and exclusion criteria were the same as the ongoing silibinin trial: Age >2-years-old; history of eating foraged mushrooms; gastrointestinal symptoms within 48 h of mushroom ingestion; and aminotransferases above the upper limit of normal within 48 h after ingestion. Each original participating PCC confirmed eligibility, diagnosis, treatment, and outcome on included cases.Results: During the study period, 8,953 mushroom exposures were reported to NPDS, of which 296 met inclusion criteria. The PCC survey response rate was 60% (28/47 PCCs), and the individual case response rate was 59% (174/296). Twenty-six cases were subsequently excluded leaving 148 included cases. The overall mortality rate was 8.8% (13/148). Mortality in silibinin/silymarin-treated vs untreated cases was 9.5% (4/42), vs 8.5% (9/106), respectively. A mycologist identified mushrooms in 16.9% of cases (25/148), of which 80% (20/25) were cyclopeptide-containing. Among these confirmed cases, the mortality rate was 10% (1/10) in both silibinin/silymarin-treated and untreated cases.Conclusions: The contemporary mortality rate of patients with presumed cyclopeptide-mushroom poisoning is only 8.8%. This likely represents improved supportive care for patients with acute liver injury and should be considered the current standard for historical controls in the United States.

Introduction: Suicide attempts by poisoning are increasing and suicide occurrence may be associated with seasonality. We performed a retrospective analysis of poisoning exposure data from a single Poison Control Center (PCC) to determine if suicide attempts were associated with season, day of the week, and/or US holidays.Methods: We analyzed exposure cases identified as "intentional overdose - suspected suicide attempt" over 2009-2012. We used singular spectrum analysis (SSA) to detect cyclic patterns in the data and then performed Poisson regression and t-tests to determine if the number of cases were associated with season, day of the week, and US holidays.Results: There were 42,578 cases of "intentional overdose - suspected suicide" during the study period. Singular Spectrum Analysis (SSA) showed that the number of cases associated with poisoning suicide attempts peaked in the Spring and dipped in the Fall. Regression analysis showed higher numbers of suspected suicide attempts from intentional overdose in spring compared with winter by 1.07 times (p = 0.003), and on Sunday (p < 0.001), Monday (p < 0.001), and Thursday (p = 0.02) compared with Saturday by at least 1.09 times. No significant difference was seen for most holidays except for lower numbers of cases around Christmas (3 days before and after; 22.0 vs. 32.3 on control dates, p < 0.001).Conclusions: Suicide attempts by poisoning are associated with season of the year and some days of the week. Further research is required determine reasons for these associations and implementation of public health interventions.

Internet-facilitated self-diagnosis and treatment is becoming more prevalent, putting individuals at risk of toxicity when drugs are acquired without medical oversight. We report a patient with delusional parasitosis who consumed veterinary albendazole purchased on the Internet, leading to pancytopenia, transaminase elevation, and alopecia. A 53-year-old man was sent to the emergency department (ED) by his gastroenterologist because of abnormal laboratory results. The patient had chronic abdominal pain and believed he was infected with parasites. He purchased two bottles of veterinary-grade albendazole on the Internet, and over the 3 weeks before his ED visit, he consumed 113.6 g of albendazole (a normal maximal daily dose is 800 mg). Five days before admission, he noticed hair loss and a rash on his face. His examination was notable for significant scalp hair loss and hyperpigmentation along the jaw line. Laboratory studies were remarkable for pancytopenia (most notably a WBC of 0.4 × 10³ cells/mm³, with an absolute neutrophil count (ANC) of 0 × 10³ cells/mm³) and transaminase elevation (AST 268 IU/L, ALT 89 IU/L). He developed a fever and was treated with antibiotics and colony-stimulating factors for presumed neutropenic bacteremia. Over the course of 1 week, his hepatic function normalized and his ANC increased to 3,000 × 10³ cells/mm³. Serial albendazole and albendazole sulfoxide concentrations were measured in serum and urine by liquid chromatography-quadruple time-of-flight mass spectrometry. On day 2, his serum concentrations were 20.7 ng/mL and 4,257.7 ng/mL for albendazole and albendazole sulfoxide, respectively. A typical peak therapeutic concentration for albendazole sulfoxide occuring at 2-5 hours post-ingestion is 220-1,580 ng/mL. Known adverse effects of albendazole include alopecia, transaminase elevation, and neutropenia. Pancytopenia leading to death from septic shock is reported. In our patient, prolonged use of high-dose albendazole resulted in a significant body burden of albendazole and albendazole sulfoxide, leading to pancytopenia, transaminase elevation, and alopecia. He recovered with supportive therapy.

Objective: Hyperthermia is a life-threatening complication of agitated delirium, and a potential consequence of sympathomimetic, anticholinergic, or oxidative phosphorylation uncoupling xenobiotics. Failure to promptly cool a hyperthermic patient leads to morbid sequelae, including rhabdomyolysis, acute kidney injury, ischemic hepatitis (shock liver), disseminated intravascular coagulation, and possibly death. The primary objective of this study is to assess one Poison Control Center's (PCC) experience with hyperthermic patients, specifically as it relates to the use of ice or water bath treatment. Secondary objectives include characterizing mortality rate, ambient temperatures at the time of presentation, and initial laboratory abnormalities.
Method(s): This is a retrospective analysis of data from a single PCC from 2014 to 2019. A structured query language search (SQL) of Toxicall

Objective: We present a patient who developed prolonged coma following treatment of ethanol withdrawal with large doses of diazepam and demonstrated prolonged elimination toxicokinetics. Case report: A 68-year-old man who drank 5-6 alcoholic beverages/day was admitted for an elective transcatheter aortic valve replacement. Two days post-procedure, he developed agitation and was presumptively treated for ethanol withdrawal with diazepam (470 mg IV over 24 hours). He remained comatose for four days prompting a toxicology consult. On day 7 of persistent coma from presumed benzodiazepine excess, flumazenil (0.5 mg) was administered; he opened his eyes for the first time, began speaking, and answering simple questions, but 30 minutes later was comatose again. Flumazenil infusion 0.25mg/h was trialed with unclear effect. His hospitalization was complicated by gastrointestinal bleeding and mild ischemic stroke deemed noncontributory to his clinical status. The flumazenil infusion was discontinued 1 week later. His evaluation was extensive (brain magnetic resonance imaging and computerised tomography, lumbar puncture, and blood cultures) and unremarkable. On hospital week 4, he became only gradually more awake, and was eventually discharged to a rehabilitation facility on hospital week 6, awake, conversive but still confused. Six weeks later, he was discharged home fully recovered. He remains amnestic to his hospitalization. Serum diazepam and nordiazepam concentrations were determined via liquid-chromatography mass-spectrometry. Concentrations obtained four days after the last dose were: diazepam 963 mug/L (therapeutic: 200-1000 mug/L) and nordiazepam 240 mug/L (therapeutic: 100-1500 mug/L). Elimination kinetics were calculated with apparent half-lives of 294 hours and 797 hours for diazepam and nordiazepam, respectively. Genotyping of CYP3A4 and CYP2C19, the two primary metabolizers of diazepam, demonstrated no abnormalities.
Conclusion(s): Diazepam demonstrated extremely atypical elimination kinetics despite normal renal and hepatic function. Acute tolerance which is expected after prolonged benzodiazepine exposure was not clearly demonstrated. The relationship between his serum concentration and clinical status is unclear at this time