Faculty Bibliography

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

INTRODUCTION/BACKGROUND:The goals of this study are to describe clinical characteristics and risk factors for metabolic acidosis with hyperlactatemia in emergency department (ED) patients with acute metformin overdose. METHODS:This was a secondary analysis of data from a retrospective observational cohort of adult ED patients presenting with acute drug overdose at two tertiary care hospitals over 5 years. The primary outcomes were: (1) hyperlactatemia, defined as a lactate concentration ≥ 2 mmol/L at any point during hospital admission and, (2) metformin associated lactic acidosis (MALA), defined as a lactate concentration ≥ 5 mmol/L and pH <7.35 at any point during hospital admission. RESULTS:We screened 3739 acute overdoses; 2872 met eligibility, 56 self-reported metformin overdose (57% female, mean age 55.8). Of these, 39 had measured lactate values. There was a high incidence of hyperlactatemia (56.4%); MALA was less frequent (17.9%). There were no deaths. Low serum bicarbonate was an independent clinical risk factor for hyperlactatemia (adjusted p < 0.05). Acetaminophen co-exposure was an independent clinical risk factor for MALA (OR 24.40, 95% CI 1.6-376.4). CONCLUSIONS:In ED patients with acute metformin overdose, initial hyperlactatemia is common but MALA is unusual. Acetaminophen co-exposure is a novel independent risk factor for the occurrence of MALA that deserves further investigation.

OBJECTIVES/OBJECTIVE:Although alcohol withdrawal is common, the recognition of benzodiazepine-resistant alcohol withdrawal is a relatively new concept. To provide a framework for both literature review and future research, we assessed clinicians' personal definition of resistant alcohol withdrawal. METHOD/METHODS:We developed a cross-sectional web-based survey. Administrators from collaborating toxicology and emergency medicine associations deployed the survey directly to their respective memberships. Only physicians, pharmacists, and other clinicians routinely treating alcohol withdrawal were eligible to participate. Respondents selected their preferred definition among the three most common author sources - JB Hack, NJ Benedict, D Hughes - or provided their own. Additional criteria to define resistant alcohol withdrawal were explored. RESULTS:384 individuals answered the survey. Respondents were mostly attending physicians (79%), in full-time practice (90%), in emergency medicine (70%), and from North America (90%). The majority (64%) described resistant alcohol withdrawal as a high benzodiazepine dosage. Seizures (26%) and persistent tachycardia (16%) were also main characteristics. The median dose to describe high benzodiazepine dose (n = 146) was 40 mg per hour of diazepam equivalents (IQR 20-50). Available definitions were ranked equally as the preferred one: Hack (27%); Benedict (28%); Hughes (28%). CONCLUSION/CONCLUSIONS:Our results did not identify one single preferred definition for resistant alcohol withdrawal even though a high total dose of benzodiazepine is a major component. Hourly requirements of 40 mg of diazepam equivalents or more emerged as a possible threshold. These findings serve as a base to explore consensus guidelines or future research.