Bryan S. Judge

Acetaminophen-cysteine adducts during therapeutic dosing and following overdose

BackgroundAcetaminophen-cysteine adducts (APAP-CYS) are a specific biomarker of acetaminophen exposure. APAP-CYS concentrations have been described in the setting of acute overdose, and a concentration >1.1 nmol/ml has been suggested as a marker of hepatic injury from acetaminophen overdose in patients with an ALT >1000 IU/L. However, the concentrations of APAP-CYS during therapeutic dosing, in cases of acetaminophen toxicity from repeated dosing and in cases of hepatic injury from non-acetaminophen hepatotoxins have not been well characterized. The objective of this study is to describe APAP-CYS concentrations in these clinical settings as well as to further characterize the concentrations observed following acetaminophen overdose.MethodsSamples were collected during three clinical trials in which subjects received 4 g/day of acetaminophen and during an observational study of acetaminophen overdose patients. Trial 1 consisted of non-drinkers who received APAP for 10 days, Trial 2 consisted of moderate drinkers dosed for 10 days and Trial 3 included subjects who chronically abuse alcohol dosed for 5 days. Patients in the observational study were categorized by type of acetaminophen exposure (single or repeated). Serum APAP-CYS was measured using high pressure liquid chromatography with electrochemical detection.ResultsTrial 1 included 144 samples from 24 subjects; Trial 2 included 182 samples from 91 subjects and Trial 3 included 200 samples from 40 subjects. In addition, we collected samples from 19 subjects with acute acetaminophen ingestion, 7 subjects with repeated acetaminophen exposure and 4 subjects who ingested another hepatotoxin. The mean (SD) peak APAP-CYS concentrations for the Trials were: Trial 1- 0.4 (0.20) nmol/ml, Trial 2- 0.1 (0.09) nmol/ml and Trial 3- 0.3 (0.12) nmol/ml. APAP-CYS concentrations varied substantially among the patients with acetaminophen toxicity (0.10 to 27.3 nmol/ml). No subject had detectable APAP-CYS following exposure to a non-acetaminophen hepatotoxin.ConclusionsLower concentrations of APAP-CYS are detectable after exposure to therapeutic doses of acetaminophen and higher concentrations are detected after acute acetaminophen overdose and in patients with acetaminophen toxicity following repeated exposure.

Ingestion of a newly described North American mushroom species from Michigan resulting in chronic renal failure: Cortinarius orellanosus.

Background. Some mushrooms in the genus Cortinarius are well known to cause acute and chronic renal failure. Until now, there have been no confirmed cases of renal failure due to the ingestion of a Cortinarius mushroom in North America. We describe a case of a woman who ingested mushrooms found under an oak tree in western Michigan and developed chronic renal failure. Methods. Phylogenetic analysis of the internal transcribed spacer (ITS) regions of nuclear-encoded ribosomal RNA was performed between an unconsumed sample of the Michigan specimens, a control sample of Cortinarius orellanus (JFA9859) from Europe, and other closely related ITS sequences of Cortinarius retrieved from GenBank. An additional gene region, rpb2, was also sequenced for comparison. Results. Phylogenetic analysis revealed the Michigan material to be closely related to, but distinct from, other ITS sequences of the Orellani clade in Cortinarius. Divergence is less at the rpb2 locus. No historical taxa from North America are known to match the identification of the Michigan material. Conclusion. The mushrooms ingested by the patient were confirmed to be a new species of Cortinarius closely related to C. orellanus. We introduce a newly described North American species, Cortinarius orellanosus, capable of causing renal failure after ingestion.

Antidepressant Overdose–induced Seizures

Treating patients with psychiatric problems can present numerous challenges for clinicians. The deliberate self-ingestion of antidepressants is one such challenge frequently encountered in hospitals throughout the United States. This review focuses on 1) the classes of antidepressants, their pharmacologic properties, and some of the proposed mechanism(s) for antidepressant overdose-induced seizures; 2) the evidence for seizures caused by antidepressants in overdose; 3) management strategies for patients who have intentionally or unintentionally overdosed on an antidepressant, or who have experienced an antidepressant overdose-induced seizure.

Successful treatment of flecainide-induced cardiac arrest with extracorporeal membrane oxygenation in the ED ☆

Flecainide is a class Ic antidysrhythmic agent used to prevent and treat tachydysrhythmias. Flecainide toxicity primarily causes cardiovascular and neurologic effects through sodium-channel blockade. There is scant evidence to support specific management, and recommended therapies have been extrapolated from management of other sodium-channel blocking drugs. Traditionally, these therapies have consisted of intravenous fluids, sodium bicarbonate, vasopressors, and cardiac pacing. Novel therapies include intravenous fat emulsion and venoarterial extracorporeal membrane oxygenation (VA-ECMO). A 24-year-old woman ingested her husbands flecainide and presented to the emergency department (ED) in profound shock with a wide complex bradydysrhythmia. Despite aggressive medical therapy including sodium bicarbonate, vasopressors, cardiac pacing, and intravenous fat emulsion, her condition deteriorated and she developed pulseless electrical activity (PEA) cardiac arrest refractory to standard resuscitation. Venoarterial extracorporeal membrane oxygenation was initiated in the ED, and the patient remained comatose and critically ill in the intensive care unit. Her hemodynamics and mental status recovered, but she had compartment syndrome in her left leg requiring fasciotomy. She was discontinued from VA-ECMO on hospital day 5, extubated on hospital day 6, and discharged home with excellent neurologic recovery on hospital day 19. Intravenous fat emulsion is thought to sequester the offending agent in a plasma lipid “sink,” alter ion channel permeability, and/or modify fatty acid utilization by the myocardium. The quality of evidence for intravenous fat emulsion is generally low. Venoarterial extracorporeal membrane oxygenation was used in this patient to restore organ perfusion and allow intrinsic drug metabolism and elimination. Venoarterial extracorporeal membrane oxygenation should be strongly considered for refractory shock and/or cardiac arrest secondary to flecainide toxicity.

Myeloneuropathy in a dentist.

We present a case of a 49-year-old male dentist with myeloneuropathy. He used nitrous oxide frequently in his practice, and denied recreational use. Magnetic resonance imaging (MRI) of his cervical and thoracic spinal cord demonstrated a hyperintense signal on T2 within the posterior columns. The patient was treated with vitamin B12 and l-methionine. A repeat MRI of his cervical spinal cord 3 months after hospital discharge showed complete regression of the hyperintense signal on T2 within the posterior columns.

Incidental discovery of radiopaque pills on abdominal CT in a patient with abdominal pain

We present a case in which a young female ingested several tablets of an over-the-counter cough and cold remedy over the course of a week. Pill fragments were identifiable and incidentally discovered when a CT scan of the abdomen was performed to evaluate the cause of her abdominal pain. Discovery of radiopaque pills on diagnostic imaging studies warrants further history and appropriate testing to rule out a life-threatening ingestion.

Self-Administered Ethanol Enema Causing Accidental Death

Excessive ethanol consumption is a leading preventable cause of death in the United States. Much of the harm from ethanol comes from those who engage in excessive or hazardous drinking. Rectal absorption of ethanol bypasses the first pass metabolic effect, allowing for a higher concentration of blood ethanol to occur for a given volume of solution and, consequently, greater potential for central nervous system depression. However, accidental death is extremely rare with rectal administration. This case report describes an individual with klismaphilia whose death resulted from acute ethanol intoxication by rectal absorption of a wine enema.

The Skill of Writing

Recently, I asked some of my medical toxicology colleagues: “What is the most important skill a medical toxicologist can have?” They provided a splendid range of answers: diagnosing and caring for severely ill undifferentiated patients, deductive and inductive reasoning, understanding dose–response relationships, etc. Surprisingly, no one answered “writing skills.” While many skills are essential for the successful practice of medical toxicology, I would argue that writing skills supersede all others, especially when the question is framed in light of academics. In 1975, Michael Crichton described medical writing as awkward, bad, and weak [1]. Almost four decades later, not a lot has changed. Formal instruction in writing or scientific writing is not typically part of residency or fellowship curricula. In fact, I am unaware of a single Medical Toxicology Fellowship program that currently offers formal instruction in writing, scientific writing, or peer review on a consistent basis. Polished writing skills remain vital to fulfilling our scientific mission of advancing the field and igniting ideas for further study. Why then do residency and fellowship programs place little—if any— emphasis on this important aspect of graduate medical education? Let’s face it—writing is often viewed to be an unpleasant task. For many of us, it is something that does not come easy. Teaching someone to be a better writer is even more challenging. To top things off, budding and seasoned authors alike get frustrated when their stylistic expression is quashed to meet the dull and formulaic format of many medical journals [2]. Other barriers to writing have been identified and include lack of time, no confidence, anxiety, and the inability to start or finish [3]. Although the roadblocks to effective writing seem insurmountable at times, the real challenge before us is imparting the importance and power of written communication to our legacy of learners—to spark a flame where perhaps there was none before.

A man with severe leg burns

Abstract A 52-year-old Hispanic male was transported to the emergency department after sustaining severe bilateral lower extremity burns in an electroplating factory. His examination revealed circumferential burns to the lower extremities with spotting in the perineum. The epidermis was stained green and sloughed off with gentle pressure. The underlying dermis was white and non-blanching, consistent with a full thickness burn. His feet were partially protected by his work boots where he had small areas of pink, blanchable, partial thickness burns (Fig. 1). Pertinent initial studies included a lactic acid level of 3.1 mmol/L and a creatinine of 1.02 mg/dL.Fig. 1. Lower extremity of a 52-year-old Hispanic male who sustained chemical burns after exposure to a heated chromic acid mixture. The photograph was taken 1 h after exposure. The white discoloration represents a full thickness circumferential burn. The green discoloration represents staining of the epidermis by the chemical mixture.

Toxic traveler? Latrodectus species envenomation in Michigan with refractory symptoms after antivenin administration

A 17-year-old male was envenomated on the right forearm by a black widow spider that had presumably traveled in a packaged dishwasher and been shipped from Mexico to Michigan. The patient experienced vomiting and severe pain in his abdomen and chest approximately 30 min after being bitten. He received 6000 units (1 vial) of Latrodectus antivenin intravenously about 7 h after he was envenomated. He did not experience significant improvement in his symptoms after the administration of antivenin and additional antivenin was not given. The patient was hospitalized for 7 days and still was complaining of intermittent episodes of pain in his chest and lower back 3 weeks after envenomation. To avoid prolonged symptomatology and hospitalization, additional Latrodectus antivenin should be given promptly to those individuals whose symptoms are not ameliorated after 1 vial.